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Sun DQ, Shen JQ, Tong XF, Ren YY, Yuan HY, Li YY, Wang XL, Chen SD, Zhu PW, Wang XD, Byrne CD, Targher G, Wei L, Wong VW, Tai D, Sanyal AJ, You H, Zheng MH. Liver fibrosis progression analyzed with AI predicts renal decline. JHEP Rep 2025; 7:101358. [PMID: 40321195 PMCID: PMC12048807 DOI: 10.1016/j.jhepr.2025.101358] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Revised: 02/05/2025] [Accepted: 02/10/2025] [Indexed: 05/03/2025] Open
Abstract
Background & Aims The relationship between biopsy-proven liver fibrosis progression and renal function decline in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) has not been fully elucidated. We used an automated quantitative liver fibrosis assessment (qFibrosis) technique to investigate the temporal changes in regional liver fibrosis. Methods This retrospective longitudinal study included 68 MASLD patients and their paired formalin-fixed sections of liver biopsies. One hundred eighty-four fibrosis parameters were quantified in five different hepatic regions, including portal tract, peri-portal, zone 2, peri-central and central vein regions, and qFibrosis continuous values were calculated for all samples based on 10 fibrosis parameters using qFibrosis assessment. Liver fibrosis progression (QLF+, n = 18) and regression (QLF-, n = 23) was defined as at least a 20% relative change in qFibrosis over a 23-month follow-up. Renal function decline was assessed by estimated glomerular filtration rate (eGFR) changes. Results The eGFR decline was greater in the QLF+ group (106.53 ± 13.71 ml/min/1.73 m2 vs. 105.28 ± 12.46 ml/min/1.73 m2) than in the QLF- group (110.87 ± 14.58 ml/min/1.73 m2 vs. 114.18 ± 14.81 ml/min/1.73 m2). In addition, liver fibrosis changes in the central vein and pericentral regions were more strongly associated with eGFR decline than in periportal, zone 2 and portal tract regions. We combined these parameters to construct a prediction model, which better differentiated eGFR decline (a cut-off value of qFibrosis combined index = 0.52, p <0.001). Conclusions A decline in renal function is significantly related to liver fibrosis progression in MASLD. Regional qFibrosis assessment may efficiently predict eGFR decline, thus highlighting the importance of assessing renal function in patients with MASLD with worsening liver fibrosis. Impact and implications The study shows that liver fibrosis progression assessed by qFibrosis may be associated with renal function decline, which provides a new perspective for understanding complex pathological processes. A combination of artificial intelligence and digital pathology may earlier and more precisely quantify the progression of regional liver fibrosis, thus better identifying changes in renal function. This opens the possibility of early interventions, which are essential to improve patients' outcomes.
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Affiliation(s)
- Dan-Qin Sun
- Department of Nephrology, Jiangnan University Medical Center, Wuxi, China
- Affiliated Wuxi Clinical College of Nantong University, Wuxi, China
- Wuxi No. 2 People's Hospital, Wuxi, China
| | - Jia-Qi Shen
- Department of Nephrology, Jiangnan University Medical Center, Wuxi, China
- Affiliated Wuxi Clinical College of Nantong University, Wuxi, China
- Wuxi No. 2 People's Hospital, Wuxi, China
| | - Xiao-Fei Tong
- Liver Research Center, Beijing Friendship Hospital, Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis, National Clinical Research Center of Digestive Diseases, Capital Medical University, Beijing, China
| | | | - Hai-Yang Yuan
- MAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, China
- Institute of Hepatology, Wenzhou Medical University, Wenzhou, China
| | - Yang-Yang Li
- Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | | | - Sui-Dan Chen
- Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Pei-Wu Zhu
- MAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Xiao-Dong Wang
- Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, China
| | - Christopher D. Byrne
- Southampton National Institute for Health and Care Research Biomedical Research Centre, University Hospital Southampton and University of Southampton, Southampton General Hospital, Southampton, UK
| | - Giovanni Targher
- Department of Medicine, University of Verona, Verona, Italy
- Metabolic Diseases Research Unit, IRCCS Sacro Cuore-Don Calabria Hospital, Negrar di Valpolicella, Italy
| | - Lai Wei
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Vincent W.S. Wong
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong Special Administrative Region of China
| | | | - Arun J. Sanyal
- Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, Virginia Commonwealth University School of Medicine, Richmond, VA, USA
| | - Hong You
- Liver Research Center, Beijing Friendship Hospital, Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis, National Clinical Research Center of Digestive Diseases, Capital Medical University, Beijing, China
| | - Ming-Hua Zheng
- MAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, China
- Institute of Hepatology, Wenzhou Medical University, Wenzhou, China
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Duan F, Wu J, Chang J, Peng H, Liu Z, Liu P, Han X, Sun T, Shang D, Yang Y, Li Z, Li P, Liu Y, Zhu Y, Lv Y, Guo X, Zhao Y, An Y. Deciphering endocrine function of adipose tissue and its significant influences in obesity-related diseases caused by its dysfunction. Differentiation 2025; 141:100832. [PMID: 39709882 DOI: 10.1016/j.diff.2024.100832] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Revised: 12/15/2024] [Accepted: 12/16/2024] [Indexed: 12/24/2024]
Abstract
Current research has found that adipose tissue is not only involved in energy metabolism, but also a highly active endocrine organ that secretes various adipokines, including adiponectin, leptin, resistin and apelin, which are involved in the regulation of physiology and pathology of tissues and organs throughout the body. With the yearly increasing incidence, obesity has become a risk factor for a variety of pathological changes, including inflammation and metabolic syndrome in various system (endocrine, circulatory, locomotor and central nervous system). Thus these symptoms lead to multi-organ dysfunctions, including the heart, liver, kidneys, brain and joints. An in-depth summary of the roles of adipokines in the regulation of other tissues and organs can help to provide more effective therapeutic strategies for obesity-related diseases and explore potential therapeutic targets. Therefore, this review has retrospected the endocrine function of adipose tissue under obesity and the role of dysregulated adipokine secretion in related diseases and the underlying mechanisms, in order to provide a theoretical basis for targeting adipokine-mediated systemic dysregulation.
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Affiliation(s)
- Feiyi Duan
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Jiaoyan Wu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Jiayi Chang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Haoyuan Peng
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Zitao Liu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Pengfei Liu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Xu Han
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; School of Stomatology, Henan University, Kaifeng, 475004, China
| | - Tiantian Sun
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; School of Stomatology, Henan University, Kaifeng, 475004, China
| | - Dandan Shang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Yutian Yang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Zhihao Li
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Pengkun Li
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Yixuan Liu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Yonghao Zhu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; School of Stomatology, Henan University, Kaifeng, 475004, China
| | - Yunzhi Lv
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; School of Stomatology, Henan University, Kaifeng, 475004, China
| | - Xiumei Guo
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Ying Zhao
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Yang An
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China.
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Hosain O, Clinkenbeard EL. Adiposity and Mineral Balance in Chronic Kidney Disease. Curr Osteoporos Rep 2024; 22:561-575. [PMID: 39394545 DOI: 10.1007/s11914-024-00884-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/27/2024] [Indexed: 10/13/2024]
Abstract
PURPOSE OF REVIEW Bone homeostasis is balanced between formation and resorption activities and remain in relative equilibrium. Under disease states this process is disrupted, favoring more resorption over formation, leading to significant bone loss and fracture incidence. This aspect is a hallmark for patients with chronic kidney disease mineral and bone disorder (CKD-MBD) affecting a significant portion of the population, both in the United States and worldwide. Further study into the underlying effects of the uremic microenvironment within bone during CKD-MBD are critical as fracture incidence in this patient population not only leads to increased morbidity, but also increased mortality. Lack of bone homeostasis also leads to mineral imbalance contributing to cardiovascular calcifications. One area understudied is the possible involvement of bone marrow adipose tissue (BMAT) during the progression of CKD-MBD. RECENT FINDINGS BMAT accumulation is found during aging and in several disease states, some of which overlap as CKD etiologies. Importantly, research has found presence of BMAT inversely correlates with bone density and volume. Understanding the underlying molecular mechanisms for BMAT formation and accumulation during CKD-MBD may offer a potential therapeutic avenue to improve bone homeostasis and ultimately mineral metabolism.
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Affiliation(s)
- Ozair Hosain
- Division of Biomedical Science, Marian University College of Osteopathic Medicine, Indianapolis, IN, 46022, USA
- Department of Medical and Molecular Genetics, School of Medicine, Indiana University, Indianapolis, IN, 46202, USA
| | - Erica L Clinkenbeard
- Department of Medical and Molecular Genetics, School of Medicine, Indiana University, Indianapolis, IN, 46202, USA.
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Das DS, Anupam A, Saharia GK. Association between liver fibrosis scores and short-term clinical outcomes in hospitalized chronic kidney disease patients: a prospective observational study. Front Med (Lausanne) 2024; 11:1387472. [PMID: 39228803 PMCID: PMC11368745 DOI: 10.3389/fmed.2024.1387472] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2024] [Accepted: 07/29/2024] [Indexed: 09/05/2024] Open
Abstract
Introduction In resource-constrained countries, inadequate access to healthcare and prognostic tools can be the Achilles' heel in effectively managing chronic kidney disease (CKD). There is a significant similarity in the pathogenesis of CKD and liver fibrosis. The role of liver fibrosis (LF) scores in predicting short-term clinical outcomes in hospitalized patients with CKD is unknown. Our study aimed at calculating LF scores and studying the association of liver fibrosis with short-term mortality and morbidity in CKD patients. Methods Patients aged above 15 years diagnosed with CKD as per the KDIGO criteria were enrolled. LF scores, namely, NFS, GPRI, and FIB-4 scores were calculated. Patients were followed up for a period of 28 days for good and poor composite outcomes, namely, the requirement of hemodialysis, non-invasive ventilation, prolonged hospital stay, and neurological and cardiovascular outcomes including death. Results Among 163 patients, 70.5% were below 60 years of age, 82.2% were male and 35% were diabetic. At 28-day follow up, 52.1% had poor composite outcome. The AUROC for GPRI and FIB-4 in predicting poor outcomes was 0.783 (95% CI: 0.71-0.855) (p < 0.001) and 0.62 (95% CI: 0.534-0.706) (p = 0.008), respectively. The AUROC for GPRI and NFS in predicting all-cause mortality was 0.735 (95% CI: 0.627-0.843) (p = 0.001) and 0.876 (95% CI, 0.8-0.952) (p < 0.001), respectively. Conclusion We found a positive association between LF scores and CKD outcomes in hospitalized patients. The LF scores significantly predicted poor outcomes in patients with CKD. Among the scores, GPRI was found to be a stronger predictor in predicting outcomes in both diabetic and non-diabetic patients with CKD. A high GPRI score was also associated with poor outcomes and increased mortality in both diabetics and non-diabetics.
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Affiliation(s)
- Dhriti Sundar Das
- Department of General Medicine, All India Institute of Medical Sciences (AIIMS), Bhubaneswar, Odisha, India
| | - Anurag Anupam
- Department of General Medicine, All India Institute of Medical Sciences (AIIMS), Bhubaneswar, Odisha, India
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Czaja-Stolc S, Chatrenet A, Potrykus M, Ruszkowski J, Torreggiani M, Lichodziejewska-Niemierko M, Dębska-Ślizień A, Piccoli GB, Małgorzewicz S. Adipokines and Myokines as Markers of Malnutrition and Sarcopenia in Patients Receiving Kidney Replacement Therapy: An Observational, Cross-Sectional Study. Nutrients 2024; 16:2480. [PMID: 39125361 PMCID: PMC11314363 DOI: 10.3390/nu16152480] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Revised: 07/23/2024] [Accepted: 07/24/2024] [Indexed: 08/12/2024] Open
Abstract
Chronic kidney disease (CKD) is linked to an elevated risk of malnutrition and sarcopenia, contributing to the intricate network of CKD-related metabolic disorders. Adipokines and myokines are markers and effectors of sarcopenia and nutritional status. The aim of this study was to assess whether the adipokine-myokine signature in patients on kidney replacement therapy could help identify malnutrition and sarcopenia. The study involved three groups: 84 hemodialysis (HD) patients, 44 peritoneal dialysis (PD) patients, and 52 kidney transplant recipients (KTR). Mean age was 56.1 ± 16.3 years. Malnutrition was defined using the 7-Point Subjective Global Assessment (SGA) and the Malnutrition-Inflammation Score (MIS). Sarcopenia was diagnosed based on reduced handgrip strength (HGS) and diminished muscle mass. Concentrations of adipokines and myokines were determined using the enzyme-linked immunosorbent assay (ELISA). 32.8% of all study participants were identified as malnourished and 20.6% had sarcopenia. For malnutrition, assessed using the 7-Point SGA, in ROC analysis albumin (area under the curve (AUC) 0.67 was the best single biomarker identified. In dialysis patients, myostatin (AUC 0.79) and IL-6 (AUC 0.67) had a high discrimination value for sarcopenia, and we were able to develop a prediction model for sarcopenia, including age, albumin, adiponectin, and myostatin levels, with an AUC of 0.806 (95% CI: 0.721-0.891). Adipokines and myokines appear to be useful laboratory markers for assessing malnutrition and sarcopenia. The formula we propose could contribute to a better understanding of sarcopenia and potentially lead to more effective interventions and management strategies for dialysis patients.
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Affiliation(s)
- Sylwia Czaja-Stolc
- Department of Clinical Nutrition and Dietetics, Faculty of Health Sciences, Medical University of Gdansk, 80-211 Gdansk, Poland; (S.C.-S.); (S.M.)
| | - Antoine Chatrenet
- Department of Nephrology, Centre Hospitalier du Mans, 72037 Le Mans, France; (A.C.); (M.T.); (G.B.P.)
- APCoSS—Institute of Physical Education and Sports Sciences (IFEPSA), UCO, 49136 Angers, France
| | - Marta Potrykus
- Department of Oncological, Transplant, and General Surgery, Faculty of Medicine, Medical University of Gdansk, 80-214 Gdansk, Poland
| | - Jakub Ruszkowski
- Department of Nephrology, Transplantology and Internal Medicine, Faculty of Medicine, Medical University of Gdansk, 80-214 Gdansk, Poland; (J.R.); (A.D.-Ś.)
| | - Massimo Torreggiani
- Department of Nephrology, Centre Hospitalier du Mans, 72037 Le Mans, France; (A.C.); (M.T.); (G.B.P.)
| | | | - Alicja Dębska-Ślizień
- Department of Nephrology, Transplantology and Internal Medicine, Faculty of Medicine, Medical University of Gdansk, 80-214 Gdansk, Poland; (J.R.); (A.D.-Ś.)
| | - Giorgina Barbara Piccoli
- Department of Nephrology, Centre Hospitalier du Mans, 72037 Le Mans, France; (A.C.); (M.T.); (G.B.P.)
- Department of Nephrology, University of Angers, 49035 Angers, France
| | - Sylwia Małgorzewicz
- Department of Clinical Nutrition and Dietetics, Faculty of Health Sciences, Medical University of Gdansk, 80-211 Gdansk, Poland; (S.C.-S.); (S.M.)
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Rusu CC, Kacso I, Moldovan D, Potra A, Tirinescu D, Ticala M, Orasan R, Budurea C, Anton F, Valea A, Bondor CI, Carsote M. Leptin Is Associated with Testosterone, Nutritional Markers, and Vascular Muscular Dysfunction in Chronic Kidney Disease. Int J Mol Sci 2024; 25:7646. [PMID: 39062887 PMCID: PMC11277084 DOI: 10.3390/ijms25147646] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Revised: 07/04/2024] [Accepted: 07/10/2024] [Indexed: 07/28/2024] Open
Abstract
Chronic kidney disease (CKD) causes specific hormonal disturbances, such as variations in leptin and testosterone levels and function. These disturbances can promote errors in signaling interaction and cellular information processing and can be implicated in the pathogenesis of atherosclerosis. This study investigates the factors that affect leptin in CKD patients and examines how leptin is related to markers of vascular disease. We conducted a cross-sectional study of 162 patients with CKD in pre-dialysis and dialysis stages. We recorded clinical and laboratory data, including leptin, testosterone, and subclinical atherosclerosis markers like brachial-ankle pulse wave velocity (ba PWV) in pre-dialysis CKD patients and flow-mediated vasodilation (FMD) and nitroglycerin-mediated vasodilation (NMD) in hemodialysis (HD) patients. Leptin was significantly correlated with testosterone in CKD pre-dialysis stages (p < 0.001) and also in HD (p = 0.026), with adipose tissue mass in pre-dialysis stages (p < 0.001), and also in HD (p < 0.001). In women HD patients, leptin correlated with NMD (p = 0.039; r = -0.379); in all HD patients, leptin correlated with C reactive protein (p = 0.007; r = 0.28) and parathormone (p = 0.039; r = -0.220). Our research emphasizes the connection between leptin, adipose tissue, and testosterone in all stages of CKD. Leptin was associated with NMD in HD women and correlated with inflammatory syndrome and parathyroid hormone in all HD patients.
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Affiliation(s)
- Crina Claudia Rusu
- Department of Nephrology, University of Medicine and Pharmacy "Iuliu Hatieganu" Cluj, 8 Victor Babes, Street, 400012 Cluj-Napoca, Romania
- Department of Nephrology, County Emergency Clinical Hospital Cluj, 3-5 Clinicilor Street, 400006 Cluj-Napoca, Romania
| | - Ina Kacso
- Department of Nephrology, University of Medicine and Pharmacy "Iuliu Hatieganu" Cluj, 8 Victor Babes, Street, 400012 Cluj-Napoca, Romania
- Department of Nephrology, County Emergency Clinical Hospital Cluj, 3-5 Clinicilor Street, 400006 Cluj-Napoca, Romania
| | - Diana Moldovan
- Department of Nephrology, University of Medicine and Pharmacy "Iuliu Hatieganu" Cluj, 8 Victor Babes, Street, 400012 Cluj-Napoca, Romania
- Department of Nephrology, County Emergency Clinical Hospital Cluj, 3-5 Clinicilor Street, 400006 Cluj-Napoca, Romania
| | - Alina Potra
- Department of Nephrology, University of Medicine and Pharmacy "Iuliu Hatieganu" Cluj, 8 Victor Babes, Street, 400012 Cluj-Napoca, Romania
- Department of Nephrology, County Emergency Clinical Hospital Cluj, 3-5 Clinicilor Street, 400006 Cluj-Napoca, Romania
| | - Dacian Tirinescu
- Department of Nephrology, University of Medicine and Pharmacy "Iuliu Hatieganu" Cluj, 8 Victor Babes, Street, 400012 Cluj-Napoca, Romania
- Department of Nephrology, County Emergency Clinical Hospital Cluj, 3-5 Clinicilor Street, 400006 Cluj-Napoca, Romania
| | - Maria Ticala
- Department of Nephrology, University of Medicine and Pharmacy "Iuliu Hatieganu" Cluj, 8 Victor Babes, Street, 400012 Cluj-Napoca, Romania
- Department of Nephrology, County Emergency Clinical Hospital Cluj, 3-5 Clinicilor Street, 400006 Cluj-Napoca, Romania
| | - Remus Orasan
- Nefromed Dialysis Center, 40 Ana Aslan Street, 400528 Cluj-Napoca, Romania
| | - Cristian Budurea
- Nefromed Dialysis Center, 40 Ana Aslan Street, 400528 Cluj-Napoca, Romania
| | - Florin Anton
- Department of Cardiology, University of Medicine and Pharmacy "Iuliu Hatieganu" Cluj, 8 Victor Babes, Street, 400012 Cluj-Napoca, Romania
| | - Ana Valea
- Department of Endocrinology, University of Medicine and Pharmacy "Iuliu Hatieganu" Cluj, 8 Victor Babes, Street, 400012 Cluj-Napoca, Romania
| | - Cosmina Ioana Bondor
- Department of Medical Informatics and Biostatistics, University of Medicine and Pharmacy "Iuliu Hatieganu" Cluj, 6 Pasteur Street, 400349 Cluj-Napoca, Romania
| | - Mara Carsote
- Department of Endocrinology, "Carol Davila" University of Medicine and Pharmacy, Dionisie Lupu Street, Number 37, Sector 1, 020021 Bucharest, Romania
- Department of Clinical Endocrinology V, "C.I. Parhon" National Institute of Endocrinology, Aviatorilor Ave 34-36, Sector 1, 011863 Bucharest, Romania
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Bullen AL, Fregoso-Leyva A, Katz R, Long DL, Cheung KL, Judd SE, Gutierrez OM, Ix JH, Cushman M, Rifkin DE. Proneurotensin/Neuromedin N and Risk of Incident CKD and Other Kidney Outcomes in Community-Living Individuals: The REGARDS Study. Kidney Med 2024; 6:100831. [PMID: 38774125 PMCID: PMC11107458 DOI: 10.1016/j.xkme.2024.100831] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/24/2024] Open
Abstract
Rationale & Objective Plasma proneurotensin/neuromedin N (pro-NT/NMN) is a precursor of neurotensin, a tridecapeptide linked with type 2 diabetes mellitus and other comorbid conditions associated with kidney disease. Whether pro-NT/NMN is directly associated with incident chronic kidney disease (CKD), and whether that association differs by race, is uncertain. We evaluated whether pro-NT/NMN levels were associated with increased risk of kidney outcomes. Study Design Prospective cohort. Setting & Participants Participants in Biomarker Mediators of Racial Disparities in Risk Factors, a nested cohort from the REasons for Geographic And Racial Differences in Stroke study, with available stored serum and urine samples from baseline and second visits for biomarker measurement. Exposure Baseline log-transformed pro-NT/NMN. Outcomes Incident CKD, progressive estimated glomerular filtration rate (eGFR) decline, incident albuminuria, and incident kidney failure within median follow-up time of 9.4 years. Analytical Approach Logistic regression. Results Among 3,914 participants, the mean ± SD age was 64 ± 8 (SD) years, 48% were women, and 51% were Black. Median baseline eGFR was 90 (IQR, 77-102) mL/min/1.73 m2. Each SD higher of pro-NT/NMN was associated with 9% higher odds of progressive eGFR decline (OR, 1.09; 95% CI, 1.00-1.20). There was no association observed with incident CKD (OR, 1.10; 95% CI, 0.96-1.27), incident albuminuria (OR, 1.08; 95% CI, 0.96-1.22), or incident kidney failure (OR, 1.10; 95% CI, 0.83-1.46). There were no differences in results by race or sex. Limitations Single measurement of pro-NT/NMN and limited generalizability. Conclusions Higher pro-NT/NMN was associated with progressive eGFR decline but no other manifestations of kidney disease incidence.
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Affiliation(s)
- Alexander L. Bullen
- Nephrology Section, Veterans Affairs San Diego Healthcare System, La Jolla, CA
- Division of Nephrology and Hypertension, Department of Medicine, University of California San Diego, San Diego, CA
| | | | - Ronit Katz
- Department of Obstetrics & Gynecology, University of Washington, Seattle, WA
| | - Dorothy Leann Long
- Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL
| | - Katharine L. Cheung
- Division of Nephrology, Larner College of Medicine, University of Vermont, Burlington, VT
| | - Suzanne E. Judd
- Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL
| | - Orlando M. Gutierrez
- Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL
| | - Joachim H. Ix
- Nephrology Section, Veterans Affairs San Diego Healthcare System, La Jolla, CA
- Division of Nephrology and Hypertension, Department of Medicine, University of California San Diego, San Diego, CA
| | - Mary Cushman
- Departments of Medicine and Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, VT
| | - Dena E. Rifkin
- Nephrology Section, Veterans Affairs San Diego Healthcare System, La Jolla, CA
- Division of Nephrology and Hypertension, Department of Medicine, University of California San Diego, San Diego, CA
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8
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Puspitasari M, Hidayat ARP, Wijaya W, Wardhani Y, Sattwika PD, Jonny J, Puspitawati I. Effectiveness of Combined Hemodialysis-Hemadsorption Therapy in Improving Uremic Toxin Clearance, Inflammatory Markers, and Symptoms in Maintenance Hemodialysis Patients. Blood Purif 2024; 53:732-742. [PMID: 38776889 DOI: 10.1159/000539396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Accepted: 05/14/2024] [Indexed: 05/25/2024]
Abstract
INTRODUCTION Combined hemodialysis (HD) and hemadsorption (HA) therapy has shown the highest clearance rates for middle and large-sized uremic toxin molecules and reduced mortality rates among maintenance HD (MHD) patients. This study aimed to investigate the effectiveness of combined HD and HA therapy in patients undergoing MHD. METHODS Forty patients with end-stage renal disease (ESRD) were divided into three groups: HD only (14), HD + biweekly HA (14), and HD + weekly HA (12). The duration of the study was 8 weeks. Uremic toxins (β2-microglobulin, leptin, parathyroid hormone), inflammatory markers (interleukin-6, C-reactive protein), and symptoms (appetite, pruritus, sleep quality) were assessed before the start and at the completion of therapy. Changes in the parameters were compared between the three groups. Mean differences of parameters in each group were also compared between before and after therapy. RESULTS Decrease in BUN level (-61.34 mg/dL [95% CI: -71.33 to -51.34], p < 0.0001) and pruritus score (-3.93 [95% CI: -6.89 to -0.97], p = 0.013) was significantly larger in HD + biweekly HA group compared to the others. Only HD + biweekly HA group showed significant reductions in CRP level (-0.10 mg/L [95%: -0.18 to -0.01], p = 0.034), VAS appetite score (10.43 [95% CI: 4.99-15.87], p = 0.001), and pruritus score (-3.93 [95% CI: -6.89 to -0.97], p = 0.013) after therapy. Both HD + biweekly HA (-2.79 [95% CI: -4.97 to -0.60], p = 0.016) and HD + weekly HA group (-2.33 [95% CI: -4.59 to -0.08], p = 0.044) exhibited a significant improvement in sleep quality score after therapy. CONCLUSIONS HD combined with a biweekly HA is associated with a greater reduction in BUN level and better improvement of pruritus in ESRD patients compared to HD alone. HD + biweekly HA can significantly reduce CRP levels, alleviate pruritus, improve appetite, and enhance sleep quality.
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Affiliation(s)
- Metalia Puspitasari
- Department of Internal Medicine, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
| | - Auliana Ratri Prabandari Hidayat
- Department of Internal Medicine, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
| | - Wynne Wijaya
- Department of Oncology, University of Oxford, Oxford, UK
| | - Yulia Wardhani
- Department of Internal Medicine, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
| | - Prenali Dwisthi Sattwika
- Cardiovascular Clinical Research Facility, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
| | - J Jonny
- Department of Internal Medicine, Gatot Soebroto Army Hospital, Jakarta, Indonesia
| | - Ira Puspitawati
- Department of Clinical Pathology and Laboratory Medicine, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
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9
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Carullo N, Zicarelli M, Michael A, Faga T, Battaglia Y, Pisani A, Perticone M, Costa D, Ielapi N, Coppolino G, Bolignano D, Serra R, Andreucci M. Childhood Obesity: Insight into Kidney Involvement. Int J Mol Sci 2023; 24:17400. [PMID: 38139229 PMCID: PMC10743690 DOI: 10.3390/ijms242417400] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Revised: 12/05/2023] [Accepted: 12/06/2023] [Indexed: 12/24/2023] Open
Abstract
This review examines the impact of childhood obesity on the kidney from an epidemiological, pathogenetic, clinical, and pathological perspective, with the aim of providing pediatricians and nephrologists with the most current data on this topic. The prevalence of childhood obesity and chronic kidney disease (CKD) is steadily increasing worldwide, reaching epidemic proportions. While the impact of obesity in children with CKD is less pronounced than in adults, recent studies suggest a similar trend in the child population. This is likely due to the significant association between obesity and the two leading causes of end-stage renal disease (ESRD): diabetes mellitus (DM) and hypertension. Obesity is a complex, systemic disease that reflects interactions between environmental and genetic factors. A key mechanism of kidney damage is related to metabolic syndrome and insulin resistance. Therefore, we can speculate about an adipose tissue-kidney axis in which neurohormonal and immunological mechanisms exacerbate complications resulting from obesity. Adipose tissue, now recognized as an endocrine organ, secretes cytokines called adipokines that may induce adaptive or maladaptive responses in renal cells, leading to kidney fibrosis. The impact of obesity on kidney transplant-related outcomes for both donors and recipients is also significant, making stringent preventive measures critical in the pre- and post-transplant phases. The challenge lies in identifying renal involvement as early as possible, as it is often completely asymptomatic and not detectable through common markers of kidney function. Ongoing research into innovative technologies, such as proteomics and metabolomics, aims to identify new biomarkers and is constantly evolving. Many aspects of pediatric disease progression in the population of children with obesity still require clarification. However, the latest scientific evidence in the field of nephrology offers glimpses into various new perspectives, such as genetic factors, comorbidities, and novel biomarkers. Investigating these aspects early could potentially improve the prognosis of these young patients through new diagnostic and therapeutic strategies. Hence, the aim of this review is to provide a comprehensive exploration of the pathogenetic mechanisms and prevalent pathological patterns of kidney damage observed in children with obesity.
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Affiliation(s)
- Nazareno Carullo
- Department of Health Sciences, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy; (N.C.); (M.Z.); (A.M.); (T.F.); (G.C.)
| | - Mariateresa Zicarelli
- Department of Health Sciences, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy; (N.C.); (M.Z.); (A.M.); (T.F.); (G.C.)
| | - Ashour Michael
- Department of Health Sciences, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy; (N.C.); (M.Z.); (A.M.); (T.F.); (G.C.)
| | - Teresa Faga
- Department of Health Sciences, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy; (N.C.); (M.Z.); (A.M.); (T.F.); (G.C.)
| | - Yuri Battaglia
- Department of Medicine, University of Verona, 37129 Verona, Italy;
| | - Antonio Pisani
- Department of Public Health, University Federico II of Naples, 80131 Naples, Italy;
| | - Maria Perticone
- Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy; (M.P.); (D.C.); (D.B.)
| | - Davide Costa
- Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy; (M.P.); (D.C.); (D.B.)
- Interuniversity Center of Phlebolymphology (CIFL), “Magna Graecia” University, 88100 Catanzaro, Italy;
| | - Nicola Ielapi
- Interuniversity Center of Phlebolymphology (CIFL), “Magna Graecia” University, 88100 Catanzaro, Italy;
- Department of Public Health and Infectious Disease, “Sapienza” University of Rome, 00185 Rome, Italy
| | - Giuseppe Coppolino
- Department of Health Sciences, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy; (N.C.); (M.Z.); (A.M.); (T.F.); (G.C.)
| | - Davide Bolignano
- Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy; (M.P.); (D.C.); (D.B.)
| | - Raffaele Serra
- Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy; (M.P.); (D.C.); (D.B.)
- Interuniversity Center of Phlebolymphology (CIFL), “Magna Graecia” University, 88100 Catanzaro, Italy;
| | - Michele Andreucci
- Department of Health Sciences, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy; (N.C.); (M.Z.); (A.M.); (T.F.); (G.C.)
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10
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Kreiner FF, Schytz PA, Heerspink HJL, von Scholten BJ, Idorn T. Obesity-Related Kidney Disease: Current Understanding and Future Perspectives. Biomedicines 2023; 11:2498. [PMID: 37760939 PMCID: PMC10526045 DOI: 10.3390/biomedicines11092498] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2023] [Revised: 09/07/2023] [Accepted: 09/08/2023] [Indexed: 09/29/2023] Open
Abstract
Obesity is a serious chronic disease and an independent risk factor for the new onset and progression of chronic kidney disease (CKD). CKD prevalence is expected to increase, at least partly due to the continuous rise in the prevalence of obesity. The concept of obesity-related kidney disease (OKD) has been introduced to describe the still incompletely understood interplay between obesity, CKD, and other cardiometabolic conditions, including risk factors for OKD and cardiovascular disease, such as diabetes and hypertension. Current therapeutics target obesity and CKD individually. Non-pharmacological interventions play a major part, but the efficacy and clinical applicability of lifestyle changes and metabolic surgery remain debatable, because the strategies do not benefit everyone, and it remains questionable whether lifestyle changes can be sustained in the long term. Pharmacological interventions, such as sodium-glucose co-transporter 2 inhibitors and the non-steroidal mineralocorticoid receptor antagonist finerenone, provide kidney protection but have limited or no impact on body weight. Medicines based on glucagon-like peptide-1 (GLP-1) induce clinically relevant weight loss and may also offer kidney benefits. An urgent medical need remains for investigations to better understand the intertwined pathophysiologies in OKD, paving the way for the best possible therapeutic strategies in this increasingly prevalent disease complex.
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Affiliation(s)
| | | | - Hiddo J. L. Heerspink
- Department of Clinical Pharmacy and Pharmacology, University of Groningen, 9700 RB Groningen, The Netherlands;
| | | | - Thomas Idorn
- Novo Nordisk A/S, DK-2860 Søborg, Denmark; (F.F.K.); (P.A.S.); (B.J.v.S.)
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11
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Chan CW, Lin BF. Folate Deficiency Enhanced Inflammation and Exacerbated Renal Fibrosis in High-Fat High-Fructose Diet-Fed Mice. Nutrients 2023; 15:3616. [PMID: 37630806 PMCID: PMC10458828 DOI: 10.3390/nu15163616] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Revised: 08/15/2023] [Accepted: 08/16/2023] [Indexed: 08/27/2023] Open
Abstract
The prevalence of obesity and chronic kidney disease (CKD) is increasing simultaneously and rapidly worldwide. Our previous study showed that folate deficiency increased lipid accumulation and leptin production of adipocytes. Whether folate plays a role in CKD, particularly obesity-related nephropathy remains unclear. To investigate the effects of folate deficiency on CKD in diet-induced obese mice, four groups of male C57BL/6 mice were fed either a normal-fat diet (NF) with folate (NF+f); NF without folate (NF-f); high-fat high-fructose diet (HFF) with folate (HFF+f); or HFF without folate (HFF-f) for 12 months during the study. The results showed that HFF increased not only body weight, fasting blood glucose, total cholesterol (TC), low-density lipoprotein (LDL)-cholesterol, and blood pressure, but also cytokines levels, such as interleukin (IL)-2, interferon (IFN)-γ, IL-17A/F, IL-6, monocyte chemoattractant protein (MCP)-1, and transforming growth factor (TGF)-β1. The indicators of kidney failure including urinary protein, neutrophil gelatinase-associated lipocalin (NGAL), renal type I and IV collagen deposits and leptin content, and serum creatinine were also increased by HFF. Folate-deficient diets further elevated serum TC, LDL-cholesterol, IL-6, tumor necrosis factor (TNF)-α, MCP-1, TGF-β1, and leptin, but decreased IL-10 level, and thus exacerbated renal fibrosis. To investigate the possible mechanisms of folate deficiency on renal injury, phosphorylation of pro-fibrosis signaling molecules, including signal transducer and activator of transcription (STAT)3 and small mothers against decapentaplegic (Smad)2/3, were assayed. Both HFF and folate deficiency significantly increased the phosphorylation of STAT3 and Smad2/3, suggesting synergistic effects of HFF-f on chronic renal inflammation and fibrosis. In conclusion, the results demonstrated that folate deficiency might aggravate inflammatory status and enhance renal fibrosis.
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Affiliation(s)
| | - Bi-Fong Lin
- Department of Biochemical Science and Technology, College of Life Science, National Taiwan University, Taipei 10617, Taiwan;
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12
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Nakagawa T, Hosoi T. Recent progress on action and regulation of anorexigenic adipokine leptin. Front Endocrinol (Lausanne) 2023; 14:1172060. [PMID: 37547309 PMCID: PMC10399691 DOI: 10.3389/fendo.2023.1172060] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Accepted: 07/06/2023] [Indexed: 08/08/2023] Open
Abstract
Organismal energy balance is controlled by inter-tissue communication mediated by the nervous system and hormones, the disruption of which causes metabolic syndrome exemplified by diabetes and obesity. Fat-storing adipose tissue, especially those located in subcutaneous white adipose tissue, secretes leptin in a proportion of fat mass, inhibiting the accumulation of organismal fat by suppressing appetite and promoting energy expenditure. With a prevalence of obesity that exhibits hyperleptinemia, most of the investigation on leptin has been focused on how it works and how it does not, which is expected to be a clue for treating obesity. In contrast, how it is synthesized, transported, and excreted, all of which are relevant to the homeostasis of blood leptin concentration, are not much understood. Of note, acute leptin reduction after hyperleptinemia in the context of obesity exhibited a beneficial effect on obesity and insulin sensitivity, indicating that manipulation of circulating leptin level may provide a therapeutic strategy. Technological advances such as "omics" analysis combined with sophisticated gene-engineered mice studies in the past decade enabled a deeper understanding of leptin's action in more detail. Here, we summarize the updated understanding of the action as well as regulation of leptin and point out the emerging direction of research on leptin.
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Affiliation(s)
- Tadashi Nakagawa
- Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University, Sanyo-Onoda, Yamaguchi, Japan
- Division of Cell Proliferation, ART, Graduate School of Medicine, Tohoku University, Sendai, Miyagi, Japan
| | - Toru Hosoi
- Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University, Sanyo-Onoda, Yamaguchi, Japan
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13
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Kadatane SP, Satariano M, Massey M, Mongan K, Raina R. The Role of Inflammation in CKD. Cells 2023; 12:1581. [PMID: 37371050 DOI: 10.3390/cells12121581] [Citation(s) in RCA: 96] [Impact Index Per Article: 48.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 06/02/2023] [Accepted: 06/03/2023] [Indexed: 06/29/2023] Open
Abstract
Chronic kidney disease (CKD) affects many adults worldwide. Persistent low-grade inflammation is a substantial factor in its development and progression and has correlated with increased mortality and cardiovascular problems. This low-grade inflammation is a product of dysregulation of the normal balance between pro- and anti-inflammatory markers. Various factors such as increased innate immune system activation, reactive oxygen species production, periodontal disease, dysregulation of anti-inflammatory systems and intestinal dysbiosis result in the dysregulation of this balance. Furthermore, this low-grade inflammation has down-effects such as hypertension, renal fibrosis and acceleration of renal function decline. Moreover, low-grade inflammation over time has been linked to malignancy in CKD. As CKD progresses, many patients require dialysis, which has a negative bidirectional relationship with persistent inflammation. Treatment options for inflammation in CKD are vast, including cytokine inhibitors, statins and diets. However, more research is needed to create a standardized management plan. In this review, we will examine the normal physiology of the kidney and its relationship with the immune system. We will then delve into the pathology behind persistent inflammation, the various causes of inflammation, the downstream effects of inflammation, dialysis and potential treatments for inflammation in CKD.
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Affiliation(s)
| | - Matthew Satariano
- Department of Medicine, Northeast Ohio Medical University, Rootstown, OH 44272, USA
| | - Michael Massey
- Department of Medicine, Northeast Ohio Medical University, Rootstown, OH 44272, USA
| | - Kai Mongan
- Department of Medicine, Northeast Ohio Medical University, Rootstown, OH 44272, USA
| | - Rupesh Raina
- Akron Nephrology Associates/Cleveland Clinic Akron General Medical Center, Akron, OH 44302, USA
- Department of Nephrology, Akron Children's Hospital, Akron, OH 44308, USA
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14
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Andres-Hernando A, Orlicky DJ, Cicerchi C, Kuwabara M, Garcia GE, Nakagawa T, Sanchez-Lozada LG, Johnson RJ, Lanaspa MA. High Fructose Corn Syrup Accelerates Kidney Disease and Mortality in Obese Mice with Metabolic Syndrome. Biomolecules 2023; 13:biom13050780. [PMID: 37238651 DOI: 10.3390/biom13050780] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Revised: 04/27/2023] [Accepted: 04/29/2023] [Indexed: 05/28/2023] Open
Abstract
The presence of obesity and metabolic syndrome is strongly linked with chronic kidney disease (CKD), but the mechanisms responsible for the association are poorly understood. Here, we tested the hypothesis that mice with obesity and metabolic syndrome might have increased susceptibility to CKD from liquid high fructose corn syrup (HFCS) by favoring the absorption and utilization of fructose. We evaluated the pound mouse model of metabolic syndrome to determine if it showed baseline differences in fructose transport and metabolism and whether it was more susceptible to chronic kidney disease when administered HFCS. Pound mice have increased expression of fructose transporter (Glut5) and fructokinase (the limiting enzyme driving fructose metabolism) associated with enhanced fructose absorption. Pound mice receiving HFCS rapidly develop CKD with increased mortality rates associated with intrarenal mitochondria loss and oxidative stress. In pound mice lacking fructokinase, the effect of HFCS to cause CKD and early mortality was aborted, associated with reductions in oxidative stress and fewer mitochondria loss. Obesity and metabolic syndrome show increased susceptibility to fructose-containing sugars and increased risk for CKD and mortality. Lowering added sugar intake may be beneficial in reducing the risk for CKD in subjects with metabolic syndrome.
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Affiliation(s)
- Ana Andres-Hernando
- Division of Endocrinology, Metabolism and Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
- Division of Nephrology, Rocky Mountain VA Medical Center, Aurora, CO 80045, USA
| | - David J Orlicky
- Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
| | - Christina Cicerchi
- Division of Endocrinology, Metabolism and Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
| | - Masanari Kuwabara
- Division of Cardiovascular Disease, Toranomon Hospital, Tokyo 105-8470, Japan
| | - Gabriela E Garcia
- Division of Endocrinology, Metabolism and Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
- Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
| | - Takahiko Nakagawa
- Department of Regenerative Medicine Development, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu 520-2192, Japan
| | | | - Richard J Johnson
- Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
- Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
| | - Miguel A Lanaspa
- Division of Endocrinology, Metabolism and Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
- Division of Nephrology, Rocky Mountain VA Medical Center, Aurora, CO 80045, USA
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15
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Serrano E, Shenoy P, Martinez Cantarin MP. Adipose tissue metabolic changes in chronic kidney disease. IMMUNOMETABOLISM (COBHAM (SURREY, ENGLAND)) 2023; 5:e00023. [PMID: 37128293 PMCID: PMC10144329 DOI: 10.1097/in9.0000000000000023] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Accepted: 04/04/2023] [Indexed: 05/03/2023]
Abstract
Adipose tissue is a complex organ whose functions go beyond being an energy reservoir to sustain proper body energy homeostasis. Functioning as an endocrine organ, the adipose tissue has an active role in the body's metabolic balance regulation through several secreted factors generally termed as adipokines. Thus, adipose tissue dysregulation in chronic kidney disease (CKD) can have a deep impact in the pathophysiology of diseases associated with metabolic dysregulation including metabolic syndrome, insulin resistance (IR), atherosclerosis, and even cachexia. CKD is a progressive disorder linked to increased morbidity and mortality. Despite being characterized by renal function loss, CKD is accompanied by metabolic disturbances such as dyslipidemia, protein energy wasting, chronic low-grade inflammation, IR, and lipid redistribution. Thus far, the mechanisms by which these changes occur and the role of adipose tissue in CKD development and progression are unclear. Further understanding of how these factors develop could have implications for the management of CKD by helping identify pharmacological targets to improve CKD outcomes.
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Affiliation(s)
- Eurico Serrano
- Division of Nephrology, Department of Medicine, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA
| | - Prashamsa Shenoy
- Division of Nephrology, Department of Medicine, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA
| | - Maria Paula Martinez Cantarin
- Division of Nephrology, Department of Medicine, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA
- *Correspondence: Maria Paula Martinez Cantarin, E-mail:
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16
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Coimbra S, Catarino C, Sameiro Faria M, Nunes JPL, Rocha S, Valente MJ, Rocha-Pereira P, Bronze-da-Rocha E, Bettencourt N, Beco A, Marques SHDM, Oliveira JG, Madureira J, Fernandes JC, Miranda V, Belo L, Santos-Silva A. The Association of Leptin with Left Ventricular Hypertrophy in End-Stage Kidney Disease Patients on Dialysis. Biomedicines 2023; 11:biomedicines11041026. [PMID: 37189644 DOI: 10.3390/biomedicines11041026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 03/17/2023] [Accepted: 03/22/2023] [Indexed: 03/29/2023] Open
Abstract
Left ventricular hypertrophy (LVH) is a common cardiovascular complication in end-stage kidney disease (ESKD) patients. We aimed at studying the association of LVH with adiponectin and leptin levels, cardiovascular stress/injury biomarkers and nutritional status in these patients. We evaluated the LV mass (LVM) and calculated the LVM index (LVMI) in 196 ESKD patients on dialysis; the levels of hemoglobin, calcium, phosphorus, parathyroid hormone, albumin, adiponectin, leptin, N-terminal pro B-type natriuretic peptide (NT-proBNP) and growth differentiation factor (GDF)-15 were analyzed. ESKD patients with LVH (n = 131) presented higher NT-proBNP and GDF-15, lower hemoglobin and, after adjustment for gender, lower leptin levels compared with non-LVH patients. LVH females also showed lower leptin than the non-LVH female group. In the LVH group, LVMI presented a negative correlation with leptin and a positive correlation with NT-proBNP. Leptin emerged as an independent determinant of LVMI in both groups, and NT-proBNP in the LVH group. Low hemoglobin and leptin and increased calcium, NT-proBNP and dialysis vintage are associated with an increased risk of developing LVH. In ESKD patients on dialysis, LVH is associated with lower leptin values (especially in women), which are negatively correlated with LVMI, and with higher levels of biomarkers of myocardial stress/injury. Leptin and NT-proBNP appear as independent determinants of LVMI; dialysis vintage, hemoglobin, calcium, NT-proBNP and leptin emerged as predicting markers for LVH development. Further studies are needed to better understand the role of leptin in LVH in ESKD patients.
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17
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Clinical Study of Metabolic Parameters, Leptin and the SGLT2 Inhibitor Empagliflozin among Patients with Obesity and Type 2 Diabetes. Int J Mol Sci 2023; 24:ijms24054405. [PMID: 36901837 PMCID: PMC10002958 DOI: 10.3390/ijms24054405] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 02/19/2023] [Accepted: 02/21/2023] [Indexed: 02/25/2023] Open
Abstract
Obesity is a major public health problem worldwide, and it is associated with many diseases and abnormalities, most importantly, type 2 diabetes. The visceral adipose tissue produces an immense variety of adipokines. Leptin is the first identified adipokine which plays a crucial role in the regulation of food intake and metabolism. Sodium glucose co-transport 2 inhibitors are potent antihyperglycemic drugs with various beneficial systemic effects. We aimed to investigate the metabolic state and leptin level among patients with obesity and type 2 diabetes mellitus, and the effect of empagliflozin upon these parameters. We recruited 102 patients into our clinical study, then we performed anthropometric, laboratory, and immunoassay tests. Body mass index, body fat, visceral fat, urea nitrogen, creatinine, and leptin levels were significantly lower in the empagliflozin treated group when compared to obese and diabetic patients receiving conventional antidiabetic treatments. Interestingly, leptin was increased not only among obese patients but in type 2 diabetic patients as well. Body mass index, body fat, and visceral fat percentages were lower, and renal function was preserved in patients receiving empagliflozin treatment. In addition to the known beneficial effects of empagliflozin regarding the cardio-metabolic and renal systems, it may also influence leptin resistance.
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18
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New Insights into Adiponectin and Leptin Roles in Chronic Kidney Disease. Biomedicines 2022; 10:biomedicines10102642. [PMID: 36289903 PMCID: PMC9599100 DOI: 10.3390/biomedicines10102642] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 10/14/2022] [Accepted: 10/15/2022] [Indexed: 11/16/2022] Open
Abstract
Chronic kidney disease (CKD) is commonly associated with a high burden of comorbidities and poor clinical outcomes. Malnutrition–inflammation–atherosclerosis syndrome is common in the more severe stages of CKD, suggesting a close interplay for these three comorbid conditions. Both malnutrition and obesity are associated with a disturbed adipokine profile and inflammation, contributing to a higher risk of cardiovascular disease (CVD) events. Adiponectin and leptin have important roles in carbohydrate and lipid metabolism, and in the inflammatory process. The effects of adiponectin and leptin alterations in CKD, which are usually increased, and their association with the different comorbidities found in CKD, will be focused on to understand their crosstalk with the risk of CVD events. Nonetheless, although adiponectin and leptin contribute to a higher risk of CVD events, further studies are warranted to fully clarify their roles, especially when different comorbidities exist.
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Evolving Concepts on Inflammatory Biomarkers and Malnutrition in Chronic Kidney Disease. Nutrients 2022; 14:nu14204297. [PMID: 36296981 PMCID: PMC9611115 DOI: 10.3390/nu14204297] [Citation(s) in RCA: 66] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 09/30/2022] [Accepted: 10/07/2022] [Indexed: 11/11/2022] Open
Abstract
While patient care, kidney replacement therapy, and transplantation techniques for chronic kidney disease (CKD) have continued to progress, the incidence of malnutrition disorders in CKD appears to have remained unchanged over time. However, there is now a better understanding of the underlying pathophysiology according to the disease background, disease stage, and the treatment received. In CKD patients, the increased production of proinflammatory cytokines and oxidative stress lead to a proinflammatory milieu that is at least partially responsible for the increased morbidity and mortality in this patient population. New insights into the pathogenic role of innate immunity and the proinflammatory cytokine profile, characterized, for instance, by higher levels of IL-6 and TNF-α, explain some of the clinical and laboratory abnormalities observed in these patients. In this article, we will explore currently available nutritional-inflammatory biomarkers in distinct CKD populations (hemodialysis, peritoneal dialysis, transplantation) with a view to evaluating their efficacy as predictors of malnutrition and their involvement in the common proinflammatory process. Although there is a direct relationship between inflammatory-nutritional status, signs and symptoms [e.g., protein-energy wasting (PEW), anorexia], and comorbidities (e.g., atheromatosis, atherosclerosis), we are in need of clearly standardized markers for nutritional-inflammatory assessment to improve their performance and design appropriate bidirectional interventions.
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Misch M, Puthanveetil P. The Head-to-Toe Hormone: Leptin as an Extensive Modulator of Physiologic Systems. Int J Mol Sci 2022; 23:ijms23105439. [PMID: 35628271 PMCID: PMC9141226 DOI: 10.3390/ijms23105439] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Revised: 04/30/2022] [Accepted: 05/10/2022] [Indexed: 12/12/2022] Open
Abstract
Leptin is a well-known hunger-sensing peptide hormone. The role of leptin in weight gain and metabolic homeostasis has been explored for the past two decades. In this review, we have tried to shed light upon the impact of leptin signaling on health and diseases. At low or moderate levels, this peptide hormone supports physiological roles, but at chronically higher doses exhibits detrimental effects on various systems. The untoward effects we observe with chronically higher levels of leptin are due to their receptor-mediated effect or due to leptin resistance and are not well studied. This review will help us in understanding the non-anorexic roles of leptin, including their contribution to the metabolism of various systems and inflammation. We will be able to get an alternative perspective regarding the physiological and pathological roles of this mysterious peptide hormone.
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Affiliation(s)
- Monica Misch
- Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL 60515, USA;
| | - Prasanth Puthanveetil
- Department of Pharmacology, College of Graduate Studies, Midwestern University, Downers Grove, IL 60515, USA
- Correspondence: ; Tel.: +1-630-960-3935
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21
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Inflammatory biomarkers in staging of chronic kidney disease: elevated TNFR2 levels accompanies renal function decline. Inflamm Res 2022; 71:591-602. [PMID: 35471601 DOI: 10.1007/s00011-022-01574-2] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Revised: 03/31/2022] [Accepted: 04/07/2022] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Inflammation is a common feature in the pathogenesis of chronic kidney disease (CKD), regardless of the disease cause. Our aim was to evaluate the potential of several inflammatory biomarkers in CKD diagnosis and staging. METHODS A total of 24 healthy controls and 92 pre-dialysis CKD patients with diverse etiologies, were enrolled in this study and grouped according to their CKD stage. We analysed the circulating levels of inflammatory molecules, C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), tumor necrosis factor receptor 2 (TNFR2), pentraxin 3 (PTX3) and leptin, as well as the hemogram. We studied their association with parameters of kidney function and kidney injury, to evaluate their potential as early markers of the disease and/or of its worsening, as well as their interplay. RESULTS Compared to controls, patients in CKD stages 1-2 presented significantly higher IL-6 and TNFR2 levels, and higher neutrophil-to-lymphocyte ratio. All inflammatory cytokines and acute-phase proteins showed a trend to increase up to stage 3, stabilizing or declining thereafter, save for TNFR2, which steadily increased from stage to stage. All inflammatory molecules, apart from PTX3, were negatively and significantly correlated with eGFR, with a remarkable value for TNFR2 (r = - 0.732, p < 0.001). CONCLUSION TNFR2 might be useful for an early detection of CKD, as well as for disease staging/worsening. Still, the potential value of this biomarker in disease progression warrants further investigation.
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22
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Zheng Y, Ji B, Chen S, Zhou R, Ni R. The impact of uremic toxins on Alzheimer's disease. Curr Alzheimer Res 2022; 19:104-118. [PMID: 35048807 DOI: 10.2174/1567205019666220120113305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Revised: 11/27/2021] [Accepted: 12/14/2021] [Indexed: 11/22/2022]
Abstract
Alzheimer's disease (AD) is the most common type of dementia, pathologically characterized by accumulation of senile plaques and neurofibrillary tangles. Chronic kidney disease (CKD) is highly prevalent in elderly population closely associated with occurrence of dementia. Recent epidemiological and experimental studies suggest a potential association of CKD with AD. Both diseases share a panel of identical risk factors, such as type 2 diabetes; and hypertension. However, the relationship between CKD and AD is unclear. Lower clearance of a panel of uremic toxin including cystatin-C, guanidine, and adiponectin due to CKD is implied to contribute to AD pathogenesis. In this review we summarize the current evidence from epidemiological, experimental and clinical studies on the potential contribution of uremic toxins to AD pathogenesis. We describe outstanding questions and propose an outlook on the link between uremic toxins and AD.
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Affiliation(s)
- Yuqi Zheng
- Department of Nephrology, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Bin Ji
- Department of Radiopharmacy and Molecular Imaging, School of Pharmacy, Fudan University, Shanghai, China
| | - Sijun Chen
- Department of Nephrology, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Rong Zhou
- Department of Nephrology, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Ruiqing Ni
- Institute for Regenerative Medicine, University of Zurich, Zurich, Switzerland
- Institute for Biomedical Engineering, University of Zurich & ETH Zurich, Zurich, Switzerland
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23
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Arabi T, Shafqat A, Sabbah BN, Fawzy NA, Shah H, Abdulkader H, Razak A, Sabbah AN, Arabi Z. Obesity-related kidney disease: Beyond hypertension and insulin-resistance. Front Endocrinol (Lausanne) 2022; 13:1095211. [PMID: 36726470 PMCID: PMC9884830 DOI: 10.3389/fendo.2022.1095211] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Accepted: 12/22/2022] [Indexed: 01/19/2023] Open
Abstract
Chronic kidney disease (CKD) causes considerable morbidity, mortality, and health expenditures worldwide. Obesity is a significant risk factor for CKD development, partially explained by the high prevalence of diabetes mellitus and hypertension in obese patients. However, adipocytes also possess potent endocrine functions, secreting a myriad of cytokines and adipokines that contribute to insulin resistance and induce a chronic low-grade inflammatory state thereby damaging the kidney. CKD development itself is associated with various metabolic alterations that exacerbate adipose tissue dysfunction and insulin resistance. This adipose-renal axis is a major focus of current research, given the rising incidence of CKD and obesity. Cellular senescence is a biologic hallmark of aging, and age is another significant risk factor for obesity and CKD. An elevated senescent cell burden in adipose tissue predicts renal dysfunction in animal models, and senotherapies may alleviate these phenotypes. In this review, we discuss the direct mechanisms by which adipose tissue contributes to CKD development, emphasizing the potential clinical importance of such pathways in augmenting the care of CKD.
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Affiliation(s)
- Tarek Arabi
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
- *Correspondence: Tarek Arabi,
| | - Areez Shafqat
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
| | | | | | - Hassan Shah
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
| | | | - Adhil Razak
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
| | | | - Ziad Arabi
- Division of Nephrology, Department of Medicine, King Abdulaziz Medical City, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
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24
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Myers MG, Affinati AH, Richardson N, Schwartz MW. Central nervous system regulation of organismal energy and glucose homeostasis. Nat Metab 2021; 3:737-750. [PMID: 34158655 DOI: 10.1038/s42255-021-00408-5] [Citation(s) in RCA: 82] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Accepted: 05/12/2021] [Indexed: 02/05/2023]
Abstract
Growing evidence implicates the brain in the regulation of both immediate fuel availability (for example, circulating glucose) and long-term energy stores (that is, adipose tissue mass). Rather than viewing the adipose tissue and glucose control systems separately, we suggest that the brain systems that control them are components of a larger, highly integrated, 'fuel homeostasis' control system. This conceptual framework, along with new insights into the organization and function of distinct neuronal systems, provides a context within which to understand how metabolic homeostasis is achieved in both basal and postprandial states. We also review evidence that dysfunction of the central fuel homeostasis system contributes to the close association between obesity and type 2 diabetes, with the goal of identifying more effective treatment options for these common metabolic disorders.
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Affiliation(s)
- Martin G Myers
- Departments of Medicine and Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA
| | - Alison H Affinati
- Departments of Medicine and Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA
| | - Nicole Richardson
- UW Medicine Diabetes Institute, Department of Medicine, University of Washington, Seattle, WA, USA
| | - Michael W Schwartz
- UW Medicine Diabetes Institute, Department of Medicine, University of Washington, Seattle, WA, USA.
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25
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The Causes and Potential Injurious Effects of Elevated Serum Leptin Levels in Chronic Kidney Disease Patients. Int J Mol Sci 2021; 22:ijms22094685. [PMID: 33925217 PMCID: PMC8125133 DOI: 10.3390/ijms22094685] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 04/25/2021] [Accepted: 04/27/2021] [Indexed: 12/15/2022] Open
Abstract
Leptin is an adipokine that regulates appetite and body mass and has many other pleiotropic functions, including regulating kidney function. Increased evidence shows that chronic kidney disease (CKD) is associated with hyperleptinemia, but the reasons for this phenomenon are not fully understood. In this review, we focused on potential causes of hyperleptinemia in patients with CKD and the effects of elevated serum leptin levels on patient kidney function and cardiovascular risk. The available data indicate that the increased concentration of leptin in the blood of CKD patients may result from both decreased leptin elimination from the circulation by the kidneys (due to renal dysfunction) and increased leptin production by the adipose tissue. The overproduction of leptin by the adipose tissue could result from: (a) hyperinsulinemia; (b) chronic inflammation; and (c) significant lipid disturbances in CKD patients. Elevated leptin in CKD patients may further deteriorate kidney function and lead to increased cardiovascular risk.
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26
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Hsu BG, Wang CH, Lai YH, Kuo CH, Lin YL. Elevated serum leptin levels are associated with low muscle strength and muscle quality in male patients undergoing chronic hemodialysis. Tzu Chi Med J 2021; 33:74-79. [PMID: 33505882 PMCID: PMC7821828 DOI: 10.4103/tcmj.tcmj_20_20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2020] [Revised: 03/09/2020] [Accepted: 04/08/2020] [Indexed: 01/01/2023] Open
Abstract
Objectives: Low muscle strength and poor muscle quality are highly prevalent in patients with chronic hemodialysis (HD), which lead to an increased risk of poor clinical outcomes. Leptin dysregulation is common in HD patients. Given that leptin receptors are abundant in skeletal muscle, there may be a link between leptin and muscle strength. The cross-sectional study aimed to explore the correlation of serum leptin levels with muscle strength and muscle quality in patients with chronic HD. Materials and Methods: A total of 118 chronic HD patients were included in this study. Basic characteristics, handgrip strength, body composition were assessed, and blood samples for serum leptin levels and other biochemical test were obtained. We defined skeletal muscle index (SMI) as skeletal muscle mass/height2 (kg/m2) and muscle quality as handgrip strength divided by mid-arm muscle circumference (MAMC). Patients were classified into tertile groups, according to sex-specific leptin levels. Results: We observed that patients in the higher leptin tertile tend to have a higher body weight, body mass index (BMI), body fat mass, MAMC, and SMI, while the handgrip strength and muscle quality were significantly lower. Bodyweight (r = 0.30; P = 0.001), BMI (r = 0.45; P = 0.001), body fat mass (r = 0.57;P < 0.001), and SMI (r = 0.22; P = 0.018) were positively and handgrip strength (r = −0.27; P = 0.003) and muscle quality (r = −0.35;P < 0.001) were negatively correlated with serum leptin levels, respectively. After adjusting multiple confounding factors, logarithmically transformed serum leptin levels were independently associated with handgrip strength (β = −3.29, P = 0.005) and muscle quality (β = −0.14, P = 0.009). However, gender-stratified models showed the associations were observed only in male, but not in female. Conclusion: We concluded that higher serum leptin levels are associated with low handgrip strength and poor muscle quality in male patients on chronic HD. Further studies are needed to clarify the gender differences and to evaluate the casual relationship between circulating leptin levels and muscle strength.
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Affiliation(s)
- Bang-Gee Hsu
- Division of Nephrology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.,School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Chih-Hsien Wang
- Division of Nephrology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.,School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Yu-Hsien Lai
- Division of Nephrology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
| | - Chiu-Huang Kuo
- Division of Nephrology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.,School of Post-Baccalaureate Chinese Medicine,Tzu Chi University,Hualien, Taiwan
| | - Yu-Li Lin
- Division of Nephrology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.,School of Medicine, Tzu Chi University, Hualien, Taiwan
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27
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Aydemir N, Pike MM, Alsouqi A, Headley SAE, Tuttle K, Evans EE, Milch CM, Moody KA, Germain M, Lipworth L, Himmelfarb J, Ikizler TA, Robinson-Cohen C. Effects of diet and exercise on adipocytokine levels in patients with moderate to severe chronic kidney disease. Nutr Metab Cardiovasc Dis 2020; 30:1375-1381. [PMID: 32571614 PMCID: PMC7659879 DOI: 10.1016/j.numecd.2020.04.012] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2020] [Revised: 04/06/2020] [Accepted: 04/08/2020] [Indexed: 01/07/2023]
Abstract
BACKGROUND AND AIMS Obesity is a pro-inflammatory risk factor for progression of CKD and cardiovascular disease. We hypothesized that implementation of caloric restriction and endurance exercise would improve adipocytokine profiles in patients with moderate to severe CKD. METHODS AND RESULTS We enrolled patients with moderate to severe CKD through a multi-center pilot randomized trial of diet and exercise in a 4-arm design (dietary restriction of 10%-15% reduction in caloric intake, exercise three times/week, combined diet and exercise, and control) (NCT01150851). Adipocytokines (adiponectin and leptin) were measured at the beginning and end of the study period as secondary outcomes. Treatment effect was analyzed in a multivariable model adjusted for baseline outcome values, age, gender, site and diabetes. A total of 122 participants were consented, 111 were randomized (42% female, 25% diabetic, and 91% hypertensive), 104 started intervention and 92 completed the study (Figure 1). Plasma adiponectin levels increased significantly in response to diet by 23% (95% CI: 0.2%, 49.8%, p = 0.048) among participants randomized to the caloric restriction and usual activity arm but not to exercise, whereas circulating leptin did not change by either treatment. CONCLUSION Our data suggest that dietary caloric restriction increases plasma adiponectin levels in stage 3-4 CKD patients, with limited effect on leptin levels. These findings suggest the potential for improving the metabolic milieu of CKD with moderate calorie restriction.
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Affiliation(s)
- Nihal Aydemir
- Hitit University Medical School, Nephrology Department, Corum, Turkey
| | - Mindy M Pike
- Vanderbilt O'Brien Kidney Center, Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Aseel Alsouqi
- Vanderbilt O'Brien Kidney Center, Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Samuel A E Headley
- Department of Exercise Science and Athletic Training, Springfield College, Springfield, MA, USA
| | - Katherine Tuttle
- Kidney Research Institute, Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA, USA; Providence Medical Research Center, Providence Health Care, Spokane, WA, USA
| | - Elizabeth E Evans
- Department of Exercise Science and Athletic Training, Springfield College, Springfield, MA, USA
| | - Charles M Milch
- Department of Exercise Science and Athletic Training, Springfield College, Springfield, MA, USA
| | - Kelsey A Moody
- Department of Exercise Science and Athletic Training, Springfield College, Springfield, MA, USA
| | - Michael Germain
- Department of Nephrology, Bay State Medical Center, Springfield, MA, USA
| | - Loren Lipworth
- Vanderbilt O'Brien Kidney Center, Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Jonathan Himmelfarb
- Kidney Research Institute, Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA, USA
| | - T A Ikizler
- Vanderbilt O'Brien Kidney Center, Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Cassianne Robinson-Cohen
- Vanderbilt O'Brien Kidney Center, Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
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Abstract
Cardiovascular disease and infections are major causes for the high incidence of morbidity and mortality of patients with chronic kidney disease. Both complications are directly or indirectly associated with disturbed functions or altered apoptotic rates of polymorphonuclear leukocytes, monocytes, lymphocytes, and dendritic cells. Normal responses of immune cells can be reduced, leading to infectious diseases or pre-activated/primed, giving rise to inflammation and subsequently to cardiovascular disease. This review summarizes the impact of kidney dysfunction on the immune system. Renal failure results in disturbed renal metabolic activities with reduced renin, erythropoietin, and vitamin D production, which adversely affects the immune system. Decreased kidney function also leads to reduced glomerular filtration and the retention of uremic toxins. A large number of uremic toxins with detrimental effects on immune cells have been identified. Besides small water-soluble and protein-bound compounds originating from the intestinal microbiome, several molecules in the middle molecular range, e.g., immunoglobulin light chains, retinol-binding protein, the neuropeptides Met-enkephalin and neuropeptide Y, endothelin-1, and the adipokines leptin and resistin, adversely affect immune cells. Posttranslational modifications such as carbamoylation, advanced glycation products, and oxidative modifications contribute to uremic toxicity. Furthermore, high-density lipoprotein from uremic patients has an altered protein profile and thereby loses its anti-inflammatory properties.
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Affiliation(s)
- Gerald Cohen
- Department of Nephrology and Dialysis, Medical University of Vienna, Vienna A-1090, Austria
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29
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Ribeiro MCCB, Vogt BP, Vannini FCD, Caramori JCT. Role of parathyroid hormone in anorexia on maintenance hemodialysis patients. Clin Nutr ESPEN 2019; 34:137-141. [PMID: 31677704 DOI: 10.1016/j.clnesp.2019.07.008] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2019] [Revised: 06/24/2019] [Accepted: 07/19/2019] [Indexed: 12/24/2022]
Abstract
BACKGROUND AND AIM Anorexia, which is a common condition in patients on hemodialysis (HD), is characterized by impaired appetite, a subjective condition that hinders anorexia diagnosis. Anorexia is frequently associated with protein energy wasting and inflammation, increasing morbidity and mortality risk. The aim of the study was to evaluate the association between appetite and nutritional, inflammatory, hormonal, and dietary intake parameters in patients on maintenance HD. METHODS Cross-sectional study with clinical, laboratory, and anthropometric parameters, body composition, muscle function, and dietary intake assessment. To evaluate appetite, a three simple questions questionnaire previously validated was used. After appetite classification, the sample was dichotomized in "normal appetite" and "impaired appetite" and compared. Multiple logistic regression was used to identify association between variables and outcome. RESULTS 125 patients on HD were included, aged 60.6 ± 14.12 years old, median HD vintage 35.5 months. In dichotomized sample, 78.4% patients showed "normal appetite", and 21.6% "impaired appetite". "Impaired appetite" was independently associated with increased serum PTH (OR 1.001; 95% CI 1.000-1.002; p = 0.03), low zinc intake (OR 0.860; 95% CI 0.746-0.991; p = 0.03) and lower urea serum (OR 0.982; 95% CI 0.965-0.999; p = 0.04). Both groups showed insufficient dietary intake. CONCLUSIONS Appetite was independently associated with increased serum of PTH, low serum concentration of urea, and low zinc intake which may infer association of appetite with mineral bone disease, protein intake and zinc deficiency.
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Affiliation(s)
| | - Barbara Perez Vogt
- Universidade Federal de Uberlândia, Faculdade de Medicina, Uberlândia, Minas Gerais, Brazil
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30
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Bagińska JO, Liszewska A, Wasilewska A, Korzeniecka-Kozerska A. The role of appetite-regulating hormones: Ghrelin and leptin in the nutritional status of children with neurogenic bladder due to myelomeningocele. J Paediatr Child Health 2019; 55:928-931. [PMID: 30488610 DOI: 10.1111/jpc.14314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2018] [Revised: 09/14/2018] [Accepted: 10/29/2018] [Indexed: 11/29/2022]
Abstract
AIM We wanted to investigate serum levels of ghrelin and leptin - appetite-regulating hormones - and their correlation with the nutritional status of children with neurogenic bladder (NB) due to myelomeningocele (MMC) in comparison to healthy individuals. METHODS This prospective analysis was conducted on 67 children with NB after MMC and 20 healthy children. Children's medical charts were analysed to determine age, gender, anthropometric measurements, body mass index (BMI), activity assessment using Hoffer's scale and renal function parameters. Serum total ghrelin and leptin levels were measured using the enzyme-linked immunosorbent assay. RESULTS There were no differences in the age, gender, weight and BMI between the studied groups. Median serum levels of ghrelin and leptin were higher compared with the reference group. A significant negative correlation between serum leptin concentration and Hoffer's scale was found in children with NB. CONCLUSIONS Elevated levels of leptin and ghrelin could be considered factors influencing nutritional status in children with NB due to MMC. Children with NB after MMC may have disturbed endocrine regulation of energy homeostasis. Physical activity may be the factor that affects serum leptin concentration.
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Affiliation(s)
- Joanna O Bagińska
- Department of Pediatric Nephrology, Medical University of Białystok, Białystok, Poland
| | - Alicja Liszewska
- Department of Pediatric Nephrology, Medical University of Białystok, Białystok, Poland
| | - Anna Wasilewska
- Department of Pediatric Nephrology, Medical University of Białystok, Białystok, Poland
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31
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Nakanishi T, Kuragano T, Nanami M, Nagasawa Y, Hasuike Y. Misdistribution of iron and oxidative stress in chronic kidney disease. Free Radic Biol Med 2019; 133:248-253. [PMID: 29958932 DOI: 10.1016/j.freeradbiomed.2018.06.025] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2018] [Revised: 06/19/2018] [Accepted: 06/21/2018] [Indexed: 12/17/2022]
Abstract
Chronic kidney disease (CKD) patients have an extremely high risk of developing cardiovascular diseases (CVD) compared to the general population. Systemic inflammation associated with oxidative stress could be an important determinant of morbidity and mortality associated with CVD. We suspected that dysregulation of iron metabolism should be considered in these patients. Anemia is prevalent in CKD patients and is often treated with erythropoiesis-stimulating agents (ESAs) and iron. In addition, iron administration sometimes causes iron overdose. Excessive iron in the cytosol and mitochondria can accelerate the formation of a highly toxic reactive oxygen species, hydroxyl radicals, which damage lipids, proteins, and DNA. In this review, we propose the following four major reasons for oxidative stress in CKD patients: 1) iron is sequestered in cells by proinflammatory cytokines and hepcidin; 2) the reduction in frataxin increases "free" iron in mitochondria; 3) the accumulation of 5-aminolevulinic acid, a heme precursor, has toxic effects on iron and mitochondrial metabolism; and 4) the elevated levels of the metabolic hormone, leptin, promote hepatic hepcidin production. Although an efficient therapy for preventing oxidative stress in these patients has not yet been well defined, we propose that ESAs for renal anemia may ameliorate these causes of oxidative stress. Further clinical trials are necessary to clarify the effectiveness of ESAs on oxidative stress in CKD patients.
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Affiliation(s)
- Takeshi Nakanishi
- Department of Nephrology, Gojinkai-Sumiyoshigawa Hospital, Japan; Department of Internal Medicine, Division of Kidney and Dialysis, Hyogo College of Medicine, Japan.
| | - Takahiro Kuragano
- Department of Internal Medicine, Division of Kidney and Dialysis, Hyogo College of Medicine, Japan.
| | - Masayoshi Nanami
- Department of Internal Medicine, Division of Kidney and Dialysis, Hyogo College of Medicine, Japan.
| | - Yasuyuki Nagasawa
- Department of Internal Medicine, Division of Kidney and Dialysis, Hyogo College of Medicine, Japan.
| | - Yukiko Hasuike
- Department of Internal Medicine, Division of Kidney and Dialysis, Hyogo College of Medicine, Japan.
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The Protective Role of Adiponectin for Lipoproteins in End-Stage Renal Disease Patients: Relationship with Diabetes and Body Mass Index. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2019; 2019:3021785. [PMID: 30911344 PMCID: PMC6397972 DOI: 10.1155/2019/3021785] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/10/2018] [Accepted: 12/10/2018] [Indexed: 12/19/2022]
Abstract
Cardiovascular disease (CVD) events are the main causes of death in end-stage renal disease (ESRD) patients on dialysis. The number and severity of CVD events remain inappropriate and difficult to explain by considering only the classic CVD risk factors. Our aim was to clarify the changes and the relationship of lipoprotein subfractions with other CVD risk factors, namely, body mass index (BMI) and adipokines, inflammation and low-density lipoprotein (LDL) oxidation, and the burden of the most prevalent comorbidities, diabetes mellitus (DM) and hypertension (HT). We studied 194 ESRD patients on dialysis and 22 controls; lipid profile, including lipoprotein subpopulations and oxidized LDL (oxLDL), C-reactive protein (CRP), adiponectin, leptin, and paraoxonase 1 activity were evaluated. Compared to controls, patients presented significantly lower levels of cholesterol, high-density lipoprotein cholesterol (HDLc), LDLc, oxLDL, and intermediate and small HDL and higher triglycerides, CRP, adiponectin, large HDL, very-low-density lipoprotein (VLDL), and intermediate-density lipoprotein- (IDL) B. Adiponectin levels correlated positively with large HDL and negatively with intermediate and small HDL, oxLDL/LDLc, and BMI; patients with DM (n = 17) and with DM+HT (n = 70), as compared to patients without DM or HT (n = 69) or only with HT (n = 38), presented significantly higher oxLDL, oxLDL/LDLc, and leptin and lower adiponectin. Obese patients (n = 45), as compared to normoponderal patients (n = 81), showed lower HDLc, adiponectin, and large HDL and significantly higher leptin, VLDL, and intermediate and small HDL. In ESRD, the higher adiponectin seems to favor atheroprotective HDL modifications and protect LDL particles from oxidative atherogenic changes. However, in diabetic and obese patients, adiponectin presents the lowest values, oxLDL/LDLc present the highest ones, and the HDL profile is the more atherogenic. Our data suggest that the coexistence of DM and adiposity in ESRD patients on dialysis contributes to a higher CVD risk, as showed by their lipid and adipokine profiles.
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Suassuna PGDA, de Paula RB, Sanders-Pinheiro H, Moe OW, Hu MC. Fibroblast growth factor 21 in chronic kidney disease. J Nephrol 2018; 32:365-377. [DOI: 10.1007/s40620-018-0550-y] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Accepted: 10/15/2018] [Indexed: 01/10/2023]
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Ray A. Cancer and comorbidity: The role of leptin in breast cancer and associated pathologies. World J Clin Cases 2018; 6:483-492. [PMID: 30397604 PMCID: PMC6212611 DOI: 10.12998/wjcc.v6.i12.483] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2018] [Revised: 08/23/2018] [Accepted: 08/30/2018] [Indexed: 02/05/2023] Open
Abstract
Obesity is an important risk factor for postmenopausal breast cancer and also a poor prognostic factor among cancer patients. Moreover, obesity is associated with a number of health disorders such as insulin resistance/type-2 diabetes mellitus, hypertension, and other cardiovascular diseases. Frequently, these health disorders exhibit as components/complications of the metabolic syndrome. Nevertheless, obesity-related diseases may coexist with postmenopausal breast cancer; and these comorbid conditions could be substantial. Therefore, it may be assumed that different diseases including breast cancer could originate from a common pathological background in excessive adipose tissue. Adipocyte-released hormone-like cytokine (or adipokine) leptin behaves differently in a normal healthy state and obesity. A growing body of evidence suggests an important role of leptin in our major obesity-related health issues such as insulin resistance, hypertension, and neoplasia. In this context, this review describes the relationships of the abovementioned pathologies with leptin.
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Affiliation(s)
- Amitabha Ray
- Lake Erie College of Osteopathic Medicine, Seton Hill University, Greensburg, PA 15601, United State
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Katsiki N, Mikhailidis DP, Banach M. Leptin, cardiovascular diseases and type 2 diabetes mellitus. Acta Pharmacol Sin 2018; 39:1176-1188. [PMID: 29877321 PMCID: PMC6289384 DOI: 10.1038/aps.2018.40] [Citation(s) in RCA: 189] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2018] [Accepted: 05/02/2018] [Indexed: 02/07/2023]
Abstract
Leptin, an adipokine that is implicated in the control of food intake via appetite suppression, may also stimulate oxidative stress, inflammation, thrombosis, arterial stiffness, angiogenesis and atherogenesis. These leptin-induced effects may predispose to the development of cardiovascular diseases. In the present review we discuss the evidence linking leptin levels with the presence, severity and/or prognosis of both coronary artery disease and non-cardiac vascular diseases such as stroke, carotid artery disease, peripheral artery disease (PAD) and abdominal aortic aneurysms (AAA) as well as with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). Leptin levels have been positively associated with the presence, severity, extent and lesion complexity of coronary atherosclerosis as well as with the presence, severity and poor clinical outcomes of both ischemic and hemorrhagic strokes. But conflicting results also exist. Furthermore, leptin was reported to independently predict common carotid intima-media thickness and carotid plaque instability. A link between hyperleptinemia and PAD has been reported, whereas limited data were available on the potential association between leptin and AAA. Elevated leptin concentrations have also been related to CKD incidence and progression as well as with insulin resistance, T2DM, micro- and macrovascular diabetic complications. Statins and antidiabetic drugs (including sitagliptin, metformin, pioglitazone, liraglutide and empagliflozin) may affect leptin levels. Further research is needed to establish the potential use (if any) of leptin as a therapeutic target in these diseases.
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Affiliation(s)
- Niki Katsiki
- Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippocration Hospital, Thessaloniki, Greece
| | - Dimitri P Mikhailidis
- Department of Clinical Biochemistry, Royal Free Hospital Campus, University College London Medical School, University College London (UCL), London, UK.
| | - Maciej Banach
- Department of Hypertension, Medical University of Lodz, Lodz, Poland
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Xu X, Tian X, Chen Y, Yang ZK, Qu Z, Dong J. Associations of Adiponectin, Leptin Levels, and the Change of Body Composition in Patients on Peritoneal Dialysis: A Prospective Cohort Study. Perit Dial Int 2018; 38:278-285. [DOI: 10.3747/pdi.2017.00177] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2017] [Accepted: 01/07/2018] [Indexed: 11/15/2022] Open
Abstract
BackgroundAlthough the association between adipokines such as adiponectin, leptin, and body composition has been noted, whether they could predict the change of fat mass and lean body mass is unknown. We aimed to examine these associations in patients on peritoneal dialysis (PD) through a prospective cohort study.MethodsBody composition (by dual-energy x-ray absorptiometry) including fat mass and lean body mass were examined at baseline and then at year 3. Serum leptin and adiponectin levels were measured. Demographic data, comorbidity, biochemical data, inflammation (high-sensitive C-reactive protein [hs-CRP]) and insulin resistance (homeostatic model assessment [HOMA-IR]) were also examined.ResultsAt baseline, serum adiponectin levels were significantly inversely correlated with weight, lean body mass index (LBMI), fat mass index (FMI), lean body mass (LBM), and fat mass (FM) in 213 prevalent patients. At year 3, FMI, LBMI, FM, and the percentage of FM (FM%) increased while the percentage of LBM (LBM%) significantly decreased despite unchanged weight and LBM among the remaining 112 patients. After adjustment for demographic data, comorbidities, hs-CRP, HOMA-IR, and daily energy intake (DEI), serum adiponectin at baseline was not associated with increases in LBMI, FMI, and FM, but independently associated with an increase in FM% and a decrease in LBM%. The predictive effect of high-serum adiponectin level on mortality disappeared after adjusting for diabetes and cardiovascular disease. Serum leptin was not associated with any changes in body composition during the follow-up, nor with the mortality in this cohort.ConclusionsA high adiponectin level could predict an increase in FM% and a decrease in LBM% during a 3-year follow-up in PD patients. Serum adiponectin could not independently predict mortality in PD patients.
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Affiliation(s)
- Xiao Xu
- Renal Division, Department of Medicine, Peking University First Hospital; Institute of Nephrology, Peking University; Key Laboratory of Renal Disease, Ministry of Health; Key Laboratory of Renal Disease, Ministry of Education; Beijing, China
| | - Xue Tian
- Renal Division, Department of Medicine, Peking University First Hospital; Institute of Nephrology, Peking University; Key Laboratory of Renal Disease, Ministry of Health; Key Laboratory of Renal Disease, Ministry of Education; Beijing, China
| | - Yuan Chen
- Renal Division, Department of Medicine, Peking University First Hospital; Institute of Nephrology, Peking University; Key Laboratory of Renal Disease, Ministry of Health; Key Laboratory of Renal Disease, Ministry of Education; Beijing, China
| | - Zhi-Kai Yang
- Renal Division, Department of Medicine, Peking University First Hospital; Institute of Nephrology, Peking University; Key Laboratory of Renal Disease, Ministry of Health; Key Laboratory of Renal Disease, Ministry of Education; Beijing, China
| | - Zhen Qu
- Renal Division, Department of Medicine, Peking University First Hospital; Institute of Nephrology, Peking University; Key Laboratory of Renal Disease, Ministry of Health; Key Laboratory of Renal Disease, Ministry of Education; Beijing, China
| | - Jie Dong
- Renal Division, Department of Medicine, Peking University First Hospital; Institute of Nephrology, Peking University; Key Laboratory of Renal Disease, Ministry of Health; Key Laboratory of Renal Disease, Ministry of Education; Beijing, China
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Vanholder R, Pletinck A, Schepers E, Glorieux G. Biochemical and Clinical Impact of Organic Uremic Retention Solutes: A Comprehensive Update. Toxins (Basel) 2018; 10:33. [PMID: 29316724 PMCID: PMC5793120 DOI: 10.3390/toxins10010033] [Citation(s) in RCA: 222] [Impact Index Per Article: 31.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2017] [Revised: 12/21/2017] [Accepted: 12/23/2017] [Indexed: 02/07/2023] Open
Abstract
In this narrative review, the biological/biochemical impact (toxicity) of a large array of known individual uremic retention solutes and groups of solutes is summarized. We classified these compounds along their physico-chemical characteristics as small water-soluble compounds or groups, protein bound compounds and middle molecules. All but one solute (glomerulopressin) affected at least one mechanism with the potential to contribute to the uremic syndrome. In general, several mechanisms were influenced for each individual solute or group of solutes, with some impacting up to 7 different biological systems of the 11 considered. The inflammatory, cardio-vascular and fibrogenic systems were those most frequently affected and they are one by one major actors in the high morbidity and mortality of CKD but also the mechanisms that have most frequently been studied. A scoring system was built with the intention to classify the reviewed compounds according to the experimental evidence of their toxicity (number of systems affected) and overall experimental and clinical evidence. Among the highest globally scoring solutes were 3 small water-soluble compounds [asymmetric dimethylarginine (ADMA); trimethylamine-N-oxide (TMAO); uric acid], 6 protein bound compounds or groups of protein bound compounds [advanced glycation end products (AGEs); p-cresyl sulfate; indoxyl sulfate; indole acetic acid; the kynurenines; phenyl acetic acid;] and 3 middle molecules [β₂-microglobulin; ghrelin; parathyroid hormone). In general, more experimental data were provided for the protein bound molecules but for almost half of them clinical evidence was missing in spite of robust experimental data. The picture emanating is one of a complex disorder, where multiple factors contribute to a multisystem complication profile, so that it seems of not much use to pursue a decrease of concentration of a single compound.
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Affiliation(s)
- Raymond Vanholder
- Nephrology Section, Department of Internal Medicine, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium.
| | - Anneleen Pletinck
- Nephrology Section, Department of Internal Medicine, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium.
| | - Eva Schepers
- Nephrology Section, Department of Internal Medicine, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium.
| | - Griet Glorieux
- Nephrology Section, Department of Internal Medicine, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium.
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Markaki A, Grammatikopoulou MG, Venihaki M, Kyriazis J, Perakis K, Stylianou K. Associations of adiponectin and leptin levels with protein-energy wasting, in end stage renal disease patients. ACTA ACUST UNITED AC 2017; 63:449-457. [PMID: 27638461 DOI: 10.1016/j.endonu.2016.07.003] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2016] [Revised: 07/03/2016] [Accepted: 07/04/2016] [Indexed: 11/29/2022]
Abstract
OBJECTIVE The aim of the study was to examine the prevalence of protein-energy wasting (PEW) in hemodialysis (HD) and peritoneal dialysis (PD) patients in our center and determine whether adiponectin and leptin are involved in the development of PEW. DESIGN Prospective (18 months). SETTING University Hospital of Heraklion, Crete, Greece. SUBJECTS Seventy-four end-stage-renal-disease patients, 47 on HD and 27 on PD. MAIN OUTCOME MEASURES At three sequential time points (baseline, 6 and 18 months) anthropometric, nutritional and inflammatory status data were collected. Serum adiponectin and leptin were also assessed at each time point. Patients were allocated to 3 strata according to PEW severity (0, 1-2 and ≥3 criteria for PEW). RESULTS Adiponectin and leptin levels were greater among PD compared to HD patients (p≤0.035). Adiponectin levels were incrementally greater across increasing strata of PEW (p≤0.002). Leptin showed the opposite trend, with lower levels in malnourished patients and higher levels in patients with zero PEW criteria (p≤0.042). Alterations of adiponectin levels during the observation period were dependent on PEW stratum (p≤0.021) and mode of dialysis (p≤0.002), after adjustment for age, dialysis vintage, gender and fat mass index. Particularly, adiponectin levels increased over time in HD patients with ≥3 criteria for PEW, whereas adiponectin levels decreased in PD patients with ≥3 criteria for PEW throughout the study. Leptin alterations over time were not affected by dialysis mode or PEW stratification. CONCLUSIONS Our study provides evidence that increased adiponectin and decreased leptin levels are independently associated with PEW and thus, poor prognosis.
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Affiliation(s)
- Anastasia Markaki
- Department of Nutrition & Dietetics, Technological Educational Institute of Crete, Sitia, Greece.
| | - Maria G Grammatikopoulou
- Department of Nutrition & Dietetics, Alexander Technological Educational Institute, Thessaloniki, Greece
| | - Maria Venihaki
- Department of Clinical Chemistry, School of Medicine, University of Crete, Heraklion, Crete, Greece
| | - John Kyriazis
- Department of Nephrology, General Hospital of Chios, Chios, Greece
| | - Kostas Perakis
- Department of Nephrology, University Hospital of Heraklion, Heraklion, Crete, Greece
| | - Kostas Stylianou
- Department of Nephrology, University Hospital of Heraklion, Heraklion, Crete, Greece
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Association of adiposity with hemoglobin levels in patients with chronic kidney disease not on dialysis. Clin Exp Nephrol 2017; 22:638-646. [PMID: 29103135 PMCID: PMC5956024 DOI: 10.1007/s10157-017-1501-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2017] [Accepted: 10/18/2017] [Indexed: 12/18/2022]
Abstract
Background In the general population, adiposity influences erythropoiesis and iron metabolism. We aimed to assess the relationships between adiposity [estimated by body mass index (BMI) and abdominal circumference (AC)] and biomarkers of erythropoiesis in patients with chronic kidney disease (CKD) not on dialysis. Methods A total of 2322 patients from the Chronic Kidney Disease Japan Cohort study were included. Patients were grouped according to BMI (low: < 18.5 kg/m2, normal: 18.5–24.5 kg/m2, and high: ≥ 25 kg/m2) and AC categories (large: ≥ 90 cm for men and ≥ 80 cm for women; small: < 90 cm and < 80 cm, respectively). Body composition and laboratory data were assessed at baseline, and at 1 and 2 years of follow-up. Results Multivariate regression analysis of the 3 time-points showed that high BMI and large AC in male patients were significantly associated with higher hemoglobin levels. Hemoglobin levels were lower in female patients with low BMI and small AC than that in female patients with normal BMI and large AC, respectively; however, hemoglobin levels plateaued above a threshold of 25 kg/m2 for BMI and 80 cm for AC. While BMI and AC were positively associated with C-reactive protein levels, they were not associated with levels of transferrin saturation, ferritin, and erythropoietin in multivariate models. Conclusions Body composition appears to be associated with erythropoiesis; however, adiposity may be only associated with increased erythropoiesis in male patients. In addition, body composition does not appear to hamper iron metabolism in CKD patients not on dialysis. Electronic supplementary material The online version of this article (10.1007/s10157-017-1501-y) contains supplementary material, which is available to authorized users.
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Niizuma S, Iwanaga Y, Yahata T, Miyazaki S. Renocardiovascular Biomarkers: from the Perspective of Managing Chronic Kidney Disease and Cardiovascular Disease. Front Cardiovasc Med 2017; 4:10. [PMID: 28321399 PMCID: PMC5337832 DOI: 10.3389/fcvm.2017.00010] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2016] [Accepted: 02/16/2017] [Indexed: 12/17/2022] Open
Abstract
Mortality among the patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) remains high because of the very high incidence of cardiovascular disease (CVD) such as coronary artery disease, cardiac hypertrophy, and heart failure. Identifying CVD in patients with CKD/ESRD remains a significant hurdle and the early diagnosis and therapy for CVD is crucial in these patients. Therefore, it is necessary for the better management to identify and utilize cardiovascular (CV) biomarkers in profiling CVD risk and enabling stratification of early mortality. This review summarizes current evidence about renocardiovascular biomarkers: CV biomarkers in patients with CKD as well as with ESRD, emphasizing on the emerging biomarkers: B-type natriuretic peptide, cardiac troponins, copeptin, the biomarker of renal injury (neutrophil gelatinase-associated lipocalin), and the mineral and bone disorder hormone/marker (fibroblast growth factor-23). Furthermore, it discusses their potential roles especially in ESRD and in future diagnostic and therapeutic strategies for CVD in the context of managing cardiorenal syndrome.
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Affiliation(s)
| | - Yoshitaka Iwanaga
- Division of Cardiology, Kindai University Faculty of Medicine , Osakasayama , Japan
| | - Takaharu Yahata
- Department of Cardiology, Yokohama Chuo Hospital , Yokohama , Japan
| | - Shunichi Miyazaki
- Division of Cardiology, Kindai University Faculty of Medicine , Osakasayama , Japan
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Sweigert PJ, Bansal VK, Hoppensteadt DA, Saluk JL, Syed DA, Fareed J. Inflammatory and Metabolic Syndrome Biomarker Analysis of Vascular Outcomes in End-stage Renal Disease. Int J Angiol 2017; 26:43-48. [PMID: 28255215 DOI: 10.1055/s-0036-1593409] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
End-stage renal disease (ESRD) presents a complex syndrome in which inflammatory and metabolic processes contribute to disease progression and development of comorbid conditions. Over $1 trillion is spent globally on ESRD care. Plasma samples collected from 83 ESRD patients prior to hemodialysis were profiled for metabolic and inflammatory biomarker concentrations. Concentrations were compared between groups with and without history of stroke, acute coronary syndrome (ACS), congestive heart failure (CHF), and coronary artery disease (CAD). The 25 patients (30.1%) with history of stroke demonstrated decreased plasma interferon-γ levels (p = 0.042) and elevated plasma resistin, interleukin (IL)-1α, and leptin levels (p = 0.008, 0.021, 0.026, respectively) when compared with ESRD patients without history of stroke. The 14 patients (16.9%) with history of ACS demonstrated elevated plasma IL-6 levels (p = 0.040) when compared with ESRD patients without history of ACS. The 30 patients (36.1%) with history of CHF demonstrated decreased plasma leptin levels (p = 0.031) and elevated plasma IL-1β levels (p = 0.042) when compared with ESRD patients without history of CHF. Finally, the 39 patients (47.0%) with history of CAD demonstrated elevated plasma IL-1α levels (p = 0.049) when compared with ESRD patients without history of CAD. Plasma biomarker concentration disturbances were observed in ESRD patients with history of stroke, ACS, CHF, and CAD when compared with ESRD patients without such history. Proinflammatory biomarker elevations were seen in stroke, ACS, CHF and CAD, while adipocytokine aberrations were observed in both stroke and CHF. These studies demonstrate that biomarker profiling of vascular comorbidities in ESRD may provide useful diagnostic and prognostic information in the management of ESRD patients.
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Affiliation(s)
| | - Vinod K Bansal
- Division of Nephrology, Department of Internal Medicine, Loyola University Medical Center, Maywood
| | - Debra A Hoppensteadt
- Division of Hemostasis and Thrombosis, Department of Pathology, Loyola University Medical Center, Maywood
| | - Jennifer L Saluk
- Stritch School of Medicine, Loyola University of Chicago, Maywood
| | - Daneyal A Syed
- Division of Hemostasis and Thrombosis, Department of Pathology, Loyola University Medical Center, Maywood
| | - Jawed Fareed
- Division of Hemostasis and Thrombosis, Department of Pathology, Loyola University Medical Center, Maywood
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Association of Increased Serum Leptin with Ameliorated Anemia and Malnutrition in Stage 5 Chronic Kidney Disease Patients after Parathyroidectomy. Sci Rep 2016; 6:27918. [PMID: 27307101 PMCID: PMC4910047 DOI: 10.1038/srep27918] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2016] [Accepted: 05/26/2016] [Indexed: 01/11/2023] Open
Abstract
Leptin is an adipokine that regulates various metabolism, but its association with secondary hyperparathyroidism (SHPT), a clinical manifestation of chronic kidney disease-mineral and bone disorder (CKD-MBD), remains obscure. Parathyroidectomy (PTX) is recommended for severe SHPT patients. Here, the associations between circulating leptin and clinical characteristics in CKD patients were investigated. Effects of PTX on leptin production were analyzed in vivo and in vitro. Controls and CKD patients had approximate serum leptin levels in that a larger proportion of CKD patients with body mass index (BMI) <23 kg/m2. Serum leptin was related to anemia, albumin, and bone metabolism disorders in CKD patients. Lower intact parathyroid hormone (PTH) was related with higher leptin in PTX patients group. Severe SHPT inhibited uremia-enhanced leptin production in 3T3-L1 adipocytes, which was attenuated after PTX. High levels of PTH were found to reduce Akt phosphorylation and leptin production in vitro but high levels of calcium and phosphorus were not. Successful PTX was found to improve anemia and malnutrition in severe SHPT patients, and this was correlated with increased circulating leptin levels via up-regulated Akt signaling in adipocytes. These findings indicated the therapeutic potential of leptin and related target pathway for improving survival and quality of life in CKD.
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Mottl AK, Divers J, Dabelea D, Maahs DM, Dolan L, Pettitt D, Marcovina S, Imperatore G, Pihoker C, Mauer M, Mayer-Davis EJ. The dose-response effect of insulin sensitivity on albuminuria in children according to diabetes type. Pediatr Nephrol 2016; 31:933-40. [PMID: 26754041 PMCID: PMC4841707 DOI: 10.1007/s00467-015-3276-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2015] [Revised: 10/25/2015] [Accepted: 10/26/2015] [Indexed: 12/17/2022]
Abstract
BACKGROUND Insulin resistance is associated with microalbuminuria among youth with diabetes mellitus. We sought to determine the dose-response effect of insulin sensitivity (IS) on the magnitude of albuminuria and whether there is a threshold below which urine albumin excretion increases. METHODS These analyses included participants from the SEARCH for Diabetes in Youth Study with incident diabetes who completed a baseline study visit (n = 2988). We estimated IS using a validated equation incorporating waist circumference, HbA1C, and fasting serum triglycerides. Multivariate regression analyses were performed to assess the effect of IS on urine albumin creatinine ratio (UACR), stratified by diabetes type. The IS threshold was then determined using segmented regressions within each diabetes type and incorporated into the multivariate model. RESULTS There was an association between IS and UACR in type 2 diabetes only (beta = -0.39; p < 0.001). There was strong statistical evidence for a threshold effect of IS score on UACR in the group of youth with type 2 (beta = 0.40; p < 0.001) but not type 1 diabetes (p = 0.3). CONCLUSIONS In cross-sectional analyses, there is a negative association between IS and UACR in youth with type 2 but not type 1 diabetes, and this association likely includes a threshold effect of IS on UACR.
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Affiliation(s)
- Amy K Mottl
- UNC Division of Nephrology and Hypertension, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
| | - Jasmin Divers
- Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - Dana Dabelea
- Department of Epidemiology, School of Public Health, University of Colorado Denver, Aurora, CO, USA
| | - David M Maahs
- Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO, USA
| | - Lawrence Dolan
- Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | | | - Santica Marcovina
- Northwest Lipid Metabolism and Diabetes Research Laboratories, Department of Medicine, University of Washington, Seattle, WA, USA
| | - Giuseppina Imperatore
- Division of Diabetes Translation, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Catherine Pihoker
- Department of Pediatrics, University of Washington, Seattle, WA, USA
| | - Michael Mauer
- Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA
- Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA
| | - Elizabeth J Mayer-Davis
- Department of Nutrition, University of North Carolina School of Public Health, Chapel Hill, NC, USA
- Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA
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Tu J, Cheung WW, Mak RH. Inflammation and nutrition in children with chronic kidney disease. World J Nephrol 2016; 5:274-282. [PMID: 27152263 PMCID: PMC4848150 DOI: 10.5527/wjn.v5.i3.274] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2015] [Revised: 09/02/2015] [Accepted: 03/09/2016] [Indexed: 02/06/2023] Open
Abstract
Chronic inflammation and nutritional imbalance are important comorbid conditions that correlate with poor clinical outcomes in children with chronic kidney disease (CKD). Nutritional disorders such as cachexia/protein energy wasting, obesity and growth retardation negatively impact the quality of life and disease progression in children with CKD. Inadequate nutrition has been associated with growth disturbances in children with CKD. On the other hand, over-nutrition and obesity are associated with poor outcomes in children with CKD. The exact mechanisms leading to these unfavorable conditions are not fully elucidated and are most likely multifactorial. In this review, we focus on the pathophysiology of nutrition disorders and inflammation and their impact on clinical outcomes in children with CKD.
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Mutsaers HAM, Stribos EGD, Glorieux G, Vanholder R, Olinga P. Chronic Kidney Disease and Fibrosis: The Role of Uremic Retention Solutes. Front Med (Lausanne) 2015; 2:60. [PMID: 26380262 PMCID: PMC4553389 DOI: 10.3389/fmed.2015.00060] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2015] [Accepted: 08/17/2015] [Indexed: 12/20/2022] Open
Abstract
Chronic kidney disease (CKD) is a major global health concern, and the uremic state is highly associated with fibrogenesis in several organs and tissues. Fibrosis is characterized by excessive production and deposition of extracellular matrix proteins with a detrimental impact on organ function. Another key feature of CKD is the retention and subsequent accumulation of solutes that are normally cleared by the healthy kidney. Several of these uremic retention solutes, including indoxyl sulfate and p-cresyl sulfate, have been suggested to be CKD-specific triggers for the development and perpetuation of fibrosis. The purpose of this brief review is to gather and discuss the current body of evidence linking uremic retention solutes to the fibrotic response during CKD, with a special emphasis on the pathophysiological mechanisms in the kidney.
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Affiliation(s)
- Henricus A M Mutsaers
- Department of Pharmaceutical Technology and Biopharmacy, University of Groningen , Groningen , Netherlands
| | - Elisabeth G D Stribos
- Department of Pharmaceutical Technology and Biopharmacy, University of Groningen , Groningen , Netherlands ; Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen , Groningen , Netherlands
| | - Griet Glorieux
- Renal Division, Department of Internal Medicine, Ghent University Hospital , Ghent , Belgium
| | - Raymond Vanholder
- Renal Division, Department of Internal Medicine, Ghent University Hospital , Ghent , Belgium
| | - Peter Olinga
- Department of Pharmaceutical Technology and Biopharmacy, University of Groningen , Groningen , Netherlands
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Jia Y, Li X, Jiang J, Sun K. Adsorption of creatinine on polyaniline-poly(styrene sulfonate) hydrogels based activated carbon particles. IRANIAN POLYMER JOURNAL 2015. [DOI: 10.1007/s13726-015-0366-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Sertoglu E, Tapan S. Proper assessment of leptin results with confounders. Scandinavian Journal of Clinical and Laboratory Investigation 2015; 75:438-9. [PMID: 25916836 DOI: 10.3109/00365513.2015.1033744] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Affiliation(s)
- Erdim Sertoglu
- Ankara Mevki Military Hospital, Anittepe Dispensary, Biochemistry Laboratory , Ankara , Turkey
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