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Nehus E, Mitsnefes M. Kidney consequences of obesity. Pediatr Nephrol 2025; 40:1879-1893. [PMID: 39680134 DOI: 10.1007/s00467-024-06623-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 11/15/2024] [Accepted: 11/15/2024] [Indexed: 12/17/2024]
Abstract
Herein, we review the devastating consequences of the worldwide obesity epidemic on kidney health and outcomes. We submit that the obesity epidemic is the most pressing public health crisis facing the nephrology community today. A historical approach has been undertaken, wherein major breakthroughs in the recognition and understanding of obesity-related kidney disease (ORKD) are highlighted. We begin with a description of the worldwide obesity epidemic followed by an account of the discovery and characterization of ORKD. A detailed summary of the pathophysiology of ORKD disease is presented, wherein we set forth the following two propositions: first, ORKD is due to a maladaptive response to caloric surplus; and second, this maladaptive response causes kidney damage via hemodynamic (hyperfiltration), hormonal (adipokine dysregulation), and lipotoxic pathways. Each of these pathways is described, with particular emphasis on the relatively recent discovery that the final stage of cellular injury in ORKD is mitochondrial oxidative damage. The prevention and treatment of ORKD are then discussed, including environmental, behavioral, pharmacologic, and surgical options. Finally, we conclude with suggestions for future research to improve early recognition and treatment of ORKD.
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Affiliation(s)
- Edward Nehus
- Department of Pediatrics, West Virginia University School of Medicine Charleston Campus, Charleston, WV, 25314, USA.
- Institute for Academic Medicine, Charleston Area Medical Center, Charleston, WV, USA.
| | - Mark Mitsnefes
- Division of Nephrology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA
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2
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Lee‐Boey JS, Tan J, Lim Z, Zaccardi F, Khunti K, Ezzati M, Gregg EW, Lim L. Obesity-related glomerulopathy: How it happens and future perspectives. Diabet Med 2025; 42:e70042. [PMID: 40226862 PMCID: PMC12080990 DOI: 10.1111/dme.70042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Revised: 03/22/2025] [Accepted: 03/29/2025] [Indexed: 04/15/2025]
Abstract
Obesity-related glomerulopathy (ORG) is an emerging complication of excess adiposity. Its incidence rises alongside the obesity pandemic. Up to 40% of individuals can be affected by ORG, irrespective of the status of glomerular filtration rate and albuminuria. ORG is a distinct histological diagnosis based on kidney biopsy, showing classical features of an enlarged glomerulus with and without focal segmental glomerulosclerosis in the perihilar region seen with all categories of obesity. About 10% of individuals with ORG may progress to end-stage kidney disease. The invasive nature of kidney biopsy highlights the need for non-invasive biomarkers for improved screening, diagnosis and risk prediction of ORG. These biomarkers may narrow the gaps in the management of ORG by improving: (1) screening, diagnosis and differentiation of ORG from non-ORG conditions; (2) risk prediction and stratification of individuals at risk of progression to end-stage kidney disease including the detection of trajectories of progression; (3) monitoring of treatment safety and effectiveness and (4) development of novel therapeutic targets. In the present review, we discussed the pathophysiology, emerging biomarkers (such as kidney injury molecule-1 [KIM-1], uromodulin, klotho, circulating microRNA-21 [miR-21]) and future treatment strategies (metabolic surgery, sodium-glucose cotransporter-2 inhibitors, incretin-based therapy and non-steroidal mineralocorticoid antagonists) of ORG.
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Affiliation(s)
| | - Jia‐Kai Tan
- Department of Medicine, Faculty of MedicineUniversiti MalayaKuala LumpurMalaysia
| | - Zhan‐Foong Lim
- Department of Medicine, Faculty of MedicineUniversiti MalayaKuala LumpurMalaysia
| | - Francesco Zaccardi
- Diabetes Research CentreUniversity of Leicester, Leicester General HospitalLeicesterUK
| | - Kamlesh Khunti
- Diabetes Research CentreUniversity of Leicester, Leicester General HospitalLeicesterUK
| | - Majid Ezzati
- Department of Epidemiology and Biostatistics, School of Public HealthImperial College LondonLondonUK
| | - Edward W. Gregg
- Department of Epidemiology and Biostatistics, School of Public HealthImperial College LondonLondonUK
- School of Population HealthRoyal College of Surgeons of IrelandDublinIreland
| | - Lee‐Ling Lim
- Department of Medicine, Faculty of MedicineUniversiti MalayaKuala LumpurMalaysia
- Department of Medicine and TherapeuticsThe Chinese University of Hong KongHong KongSARChina
- Asia Diabetes FoundationHong KongSARChina
- Baker Heart and Diabetes InstituteMelbourneAustralia
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3
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Bansal A, Chonchol M. Metabolic Dysfunction Associated Kidney Disease: Pathogenesis and Clinical Manifestations. Kidney Int 2025:S0085-2538(25)00351-5. [PMID: 40379048 DOI: 10.1016/j.kint.2025.01.044] [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: 10/28/2024] [Revised: 01/14/2025] [Accepted: 01/30/2025] [Indexed: 05/19/2025]
Abstract
In recent years, there have been significant changes in the lifestyle and eating behaviors of the population characterized by increased intake of high-calories food and a sedentary lifestyle without physical activity. The increased prevalence of overweight and obesity has led to metabolic dysfunction and their related complications, such as cardiovascular disease and chronic kidney disease (CKD). The purpose of this review is to highlight the importance, clinical features and pathogenesis of metabolic dysfunction-associated kidney disease (MDAKD). MDAKD is a term that describes kidney disease arising from metabolic dysfunction, often in the context of metabolic syndrome (MetS) and is characterized by the presence of CKD in individuals with metabolic abnormalities such as obesity, insulin resistance, diabetes mellitus, dyslipidemia, and hypertension. MDAKD includes diabetic kidney disease (DKD), obesity-related kidney disease (ORKD) and with increasing recognition of other rarer kidney diseases where metabolic dysfunction may impact progression. MDAKD is part of the spectrum of diseases whose pathogenesis is driven by metabolic dysfunction and has recently led to the proposal of new nomenclature including metabolic dysfunction associated steatotic liver disease (MASLD) and Cardio-Kidney-Metabolic Syndrome (CKM Syndrome). The new terminology of MDAKD provides additional emphasis on the pathogenic role of metabolic dysfunction on kidney disease.
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Affiliation(s)
- Anip Bansal
- Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, CO
| | - Michel Chonchol
- Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, CO.
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Kovesdy CP. Obesity and Metabolic Health in CKD. Clin J Am Soc Nephrol 2025; 20:742-754. [PMID: 40085173 PMCID: PMC12097191 DOI: 10.2215/cjn.0000000704] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Accepted: 03/04/2025] [Indexed: 03/16/2025]
Abstract
Obesity is a worldwide epidemic with a future projected growth of 40% over 10 years. Obesity increases the risk of diabetes, hypertension, and cardiovascular disease, and it also leads to higher risk of CKD, through both direct and indirect mechanisms. Although obesity is a feature of overnutrition and is associated with poor outcomes in the general population, obese individuals with CKD often display complex metabolic patterns such as sarcopenic obesity, and obesity can be associated with better survival in individuals with advanced CKD. Weight loss interventions are proven to improve glycemic control and cardiovascular risk factors, and successful weight loss is associated with improved albuminuria in patients with preexisting CKD. The long-term effects of weight loss interventions on kidney function and on survival in patients with CKD are less well studied, and hence, such interventions should be individualized.
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Affiliation(s)
- Csaba P Kovesdy
- Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee
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5
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Pati P, De Miguel C, Paul JR, Zhang D, Colson J, Allan JM, Edell CJ, Rhoads MK, Dunaway LS, Biswal SN, Zhong Y, Sedaka R, Millender-Swain T, Bailey SM, Gamble KL, Pollock DM, Pollock JS. Time-restricted feeding reduces cardiovascular disease risk in obese mice. JCI Insight 2025; 10:e160257. [PMID: 39812779 PMCID: PMC11949066 DOI: 10.1172/jci.insight.160257] [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: 03/24/2022] [Accepted: 01/02/2025] [Indexed: 01/16/2025] Open
Abstract
Disrupted feeding and fasting cycles as well as chronic high-fat diet-induced (HFD-induced) obesity are associated with cardiovascular disease risk factors. We designed studies that determined whether 2 weeks of time-restricted feeding (TRF) intervention in mice fed a chronic HFD would reduce cardiovascular disease risk factors. Mice were fed a normal diet (ND; 10% fat) ad libitum or HFD (45% fat) for 18 weeks ad libitum to establish diet-induced obesity. ND or HFD mice were continued on ad libitum diet or subjected to TRF (limiting food availability to 12 hours only during the dark phase) during the final 2 weeks of the feeding protocol. TRF improved whole-body metabolic diurnal rhythms without a change in body weight. HFD mice showed reduced blood pressure dipping compared with ND, which was restored by TRF. Further, TRF reduced aortic wall thickness, decreased aortic stiffness, as well as increased kidney tubular brush border integrity, decreased renal medullary fibrosis, and reduced renal medullary T cell inflammation in HFD mice. These findings indicate that TRF may be an effective intervention for improving vascular and kidney health in a model of established diet-induced obesity.
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Affiliation(s)
- Paramita Pati
- Section of Cardio-Renal Physiology & Medicine, Division of Nephrology, Department of Medicine
| | - Carmen De Miguel
- Section of Cardio-Renal Physiology & Medicine, Division of Nephrology, Department of Medicine
| | - Jodi R. Paul
- Division of Behavioral Neurobiology, Department of Psychiatry; and
| | - Dingguo Zhang
- Section of Cardio-Renal Physiology & Medicine, Division of Nephrology, Department of Medicine
| | - Jackson Colson
- Section of Cardio-Renal Physiology & Medicine, Division of Nephrology, Department of Medicine
| | - John Miller Allan
- Section of Cardio-Renal Physiology & Medicine, Division of Nephrology, Department of Medicine
| | - Claudia J. Edell
- Section of Cardio-Renal Physiology & Medicine, Division of Nephrology, Department of Medicine
| | - Megan K. Rhoads
- Section of Cardio-Renal Physiology & Medicine, Division of Nephrology, Department of Medicine
| | - Luke S. Dunaway
- Section of Cardio-Renal Physiology & Medicine, Division of Nephrology, Department of Medicine
| | - Sara N. Biswal
- Section of Cardio-Renal Physiology & Medicine, Division of Nephrology, Department of Medicine
| | - Yihan Zhong
- Section of Cardio-Renal Physiology & Medicine, Division of Nephrology, Department of Medicine
| | - Randee Sedaka
- Section of Cardio-Renal Physiology & Medicine, Division of Nephrology, Department of Medicine
| | - Telisha Millender-Swain
- Division of Molecular and Cellular Pathology, Department of Pathology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Shannon M. Bailey
- Division of Molecular and Cellular Pathology, Department of Pathology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Karen L. Gamble
- Division of Behavioral Neurobiology, Department of Psychiatry; and
| | - David M. Pollock
- Section of Cardio-Renal Physiology & Medicine, Division of Nephrology, Department of Medicine
| | - Jennifer S. Pollock
- Section of Cardio-Renal Physiology & Medicine, Division of Nephrology, Department of Medicine
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Kounatidis D, Vallianou NG, Stratigou T, Voukali M, Karampela I, Dalamaga M. The Kidney in Obesity: Current Evidence, Perspectives and Controversies. Curr Obes Rep 2024; 13:680-702. [PMID: 39141201 DOI: 10.1007/s13679-024-00583-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/01/2024] [Indexed: 08/15/2024]
Abstract
PURPOSE OF REVIEW As obesity and chronic kidney disease (CKD) remain a public health issue, we aim to elaborate on their complex relationship regarding pathogenetic mechanisms and therapeutic potential as well. The purpose of this review is to enhance our understanding of the interplay between obesity and CKD in order to timely diagnose and treat obesity-related CKD. RECENT FINDINGS Obesity and CKD pose significant intertwined challenges to global health, affecting a substantial portion of the population worldwide. Obesity is recognized as an independent risk factor, intricately contributing to CKD pathogenesis through mechanisms such as lipotoxicity, chronic inflammation, and insulin resistance. Recent evidence highlights additional factors including hemodynamic changes and intestinal dysbiosis that exacerbate kidney dysfunction in obese individuals, leading to histologic alterations known as obesity-related glomerulopathy (ORG). This narrative review synthesizes current knowledge on the prevalence, pathophysiology, clinical manifestations, and diagnostic strategies of obesity-related kidney disease. Furthermore, it explores mechanistic insights to delineate current therapeutic approaches, future directions for managing this condition and controversies. By elucidating the multifaceted interactions between obesity and kidney health, this review aims to inform clinical practice and stimulate further research to address this global health epidemic effectively.
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Affiliation(s)
- Dimitris Kounatidis
- Diabetes Center, First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, 11527, Athens, Greece
| | - Natalia G Vallianou
- First Department of Internal Medicine, Sismanogleio General Hospital, 15126, Athens, Greece.
| | - Theodora Stratigou
- Department of Endocrinology, Diabetes and Metabolism, European and National Expertise Center for Rare Endocrine Disorders, Evangelismos General Hospital, 10676, Athens, Greece
| | - Maria Voukali
- First Department of Internal Medicine, Sismanogleio General Hospital, 15126, Athens, Greece
| | - Irene Karampela
- Second Department of Critical Care, Medical School, Attikon General University Hospital, National and Kapodistrian University of Athens, 12462, Athens, Greece
| | - Maria Dalamaga
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527, Athens, Greece
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Chung Y, Paik B, Jeon D, Kim YJ. Obesity, kidney and metabolic bariatric surgery: a surgeon’s narrative review. METABOLISM AND TARGET ORGAN DAMAGE 2024; 4. [DOI: 10.20517/mtod.2023.51] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Excess body weight impacts kidney function in individuals with severe obesity, primarily through metabolic alterations in adipocytes, especially in visceral adipose tissue. The relationship between persistent sterile inflammation associated with obesity and the progression of obesity-related kidney disease to chronic kidney disease (CKD) is an area of growing interest. The beneficial effects of weight loss on the prevention of kidney disease and the improvement of kidney function in individuals with obesity have been well documented. Currently, the most effective weight loss strategy is metabolic bariatric surgery (MBS), which has been proven to not only prevent the progression of CKD but also reverse it. However, awareness and understanding of the impact of obesity on the kidney should also extend to the severely obese population with clinically normal renal function. The purpose of this review is to outline the current knowledge on the pathophysiology of obesity-induced kidney damage, the effects of MBS on renal function in severely obese individuals with or without CKD, and provide the current evidence on perioperative management strategies for CKD patients, including diet and nutrition.
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He HY, Feng L, You YK, Yap DYH, Pai P, Guo XH, Ren YP, Li XY. The renal histopathology of nonproteinuric kidney impairment: a three center experience. Clin Exp Med 2024; 24:236. [PMID: 39361090 PMCID: PMC11450049 DOI: 10.1007/s10238-024-01494-x] [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: 09/16/2024] [Accepted: 09/20/2024] [Indexed: 10/06/2024]
Abstract
Proteinuria is a biomarker of kidney injury that typically results from glomerular and/or tubulointerstitial disease. Whereas kidney impairment with normal urinary protein excretion is usually less focused and understudied. We conducted a retrospective review of the renal histopathology of the patients with variable degrees of unexplained renal insufficiency but with normal range proteinuria between 2014 and 2024 of three university teaching hospitals in Shenzhen city of Southern China. Patients with kidney dysfunction of undetermined or uncertain etiology and with normal urinary protein excretion (defined by a 24hr urinary protein excretion < 150 mg or spot urinary protein to creatinine ratio [PCR] < 150 mg/g) were enrolled and analyzed. In a total of 2405 patients, 53 (2.2%) fulfilled the inclusion criteria (male/female 40/13, age 47.3 ± 14.3 years) with a mean eGFR of 46.6 ± 16.8 ml/min per 1.73 m2. Glomerular disease (GD) was the most frequent pathological finding identified in 23 (43.4%) patients, while 19 (35.8%) cases showed tubulointerstitial disease (TID) and 11 (20.8%) patients exhibited small vascular disease (SVD). Patients in the TID had the lowest mean eGFR and the highest numerical 24hr urinary protein excretion among the three groups. The incidence of acute kidney injury was significantly higher in TID than in other two groups. The patients in the SVD group had the highest fraction of underlying hypertension. Kidney dysfunction with normal range proteinuria may be related with, in descending order of probablity, glomerular, tubulointerstitial and small vascular diseases. Renal biopsies were proved useful in informing therapeutic choice, long-term management and in predicting prognosis in this setting.
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Affiliation(s)
- Hai-Yan He
- Department of Nephrology, University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Ling Feng
- Department of Nephrology, Shenzhen Hospital of Southern Medical University, Shenzhen, China
| | - Yong-Ke You
- Department of Nephrology, Shenzhen University General Hospital, Shenzhen, China
| | - Desmond Y H Yap
- Department of Medicine, University of Hong Kong-Queen Mary Hospital, Pokfulam Road, Hong Kong, China
| | - Pearl Pai
- Department of Nephrology, University of Hong Kong-Shenzhen Hospital, Shenzhen, China
- Department of Medicine, University of Hong Kong-Queen Mary Hospital, Pokfulam Road, Hong Kong, China
| | - Xiao-Hua Guo
- Department of Nephrology, Shenzhen Hospital of Southern Medical University, Shenzhen, China
| | - Ye-Ping Ren
- Department of Nephrology, Shenzhen University General Hospital, Shenzhen, China
| | - Xiang-Yang Li
- Department of Nephrology, University of Hong Kong-Shenzhen Hospital, Shenzhen, China.
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Chen Y, Jin J, Zhang P, Ye R, Zeng C, Zhang Y, Chen J, Li H, Xiao H, Li Y, Guan H. Clinical Impact of Obesity on Postoperative Outcomes of Patients With Thyroid Cancer Undergoing Thyroidectomy: A 5-Year Retrospective Analysis From the US National Inpatient Sample. Cancer Med 2024; 13:e70335. [PMID: 39417377 PMCID: PMC11483747 DOI: 10.1002/cam4.70335] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Revised: 02/21/2024] [Accepted: 09/30/2024] [Indexed: 10/19/2024] Open
Abstract
BACKGROUND The clinical impact of obesity on postoperative outcomes of patients undergoing thyroidectomy remains controversial. METHODS Patients aged ≥ 18 years who were diagnosed with thyroid malignancy and underwent thyroidectomy between 2016 and 2020 were included, and divided into two groups: patients with body mass index (BMI) < 30 kg/m2 and those with BMI ≥ 30 kg/m2. Patients in the obese group were then subdivided into four groups: Group 1 (BMI 30.0-34.9 kg/m2), Group 2 (BMI 35.0-39.9 kg/m2), Group 3 (BMI 40.0-44.9 kg/m2), and Group 4 (BMI ≥ 45.0 kg/m2) to evaluate the association between degree of obesity and clinical outcomes. We performed propensity score matching, compared outcome variables between the groups, and conducted adjusted multivariate logistic regression analyses of postoperative outcomes. RESULTS A total of 6778 patients diagnosed with thyroid cancer who underwent thyroidectomy were screened, of whom 1299 (19.2%) patients were obese. Patients in the obese group had higher total hospital charges (p < 0.001) and an increased risk of overall postoperative complications (34.7% vs. 30.5%, p = 0.023). Specifically, patients in the obese group had increased odds of respiratory complication (adjusted odds ratio (aOR) 1.66, 95% confidence interval (CI) [1.26-2.19]), acute renal failure (aOR 1.87, 95% CI [1.13-3.09]), and wound complication (aOR 2.77, 95% CI [1.21-6.37]) than those in the non-obese group. Moreover, trend tests showed that the risks of unfavorable discharge, infection, acute renal failure, and respiratory complication all exhibited an upward trend with increased BMI. CONCLUSION Obesity is associated with an increased risk of postoperative complications in patients with thyroid cancer undergoing thyroidectomy. This finding suggests that obese patients should be treated with more caution during postoperative recovery.
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Affiliation(s)
- Yue Chen
- Department of Endocrinology and Diabetes CenterThe First Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina
| | - Jiewen Jin
- Department of Endocrinology and Diabetes CenterThe First Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina
| | - Pengyuan Zhang
- Department of Endocrinology and Diabetes CenterThe First Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina
| | - Runyi Ye
- Department of Breast SurgeryThe First Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouGuangdongChina
| | - Chuimian Zeng
- Department of Endocrinology and Diabetes CenterThe First Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina
- Zhongshan School of MedicineSun Yat‐sen UniversityGuangzhouChina
| | - Yilin Zhang
- Department of Endocrinology and Diabetes CenterThe First Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina
- Zhongshan School of MedicineSun Yat‐sen UniversityGuangzhouChina
| | - Junxin Chen
- Department of Endocrinology and Diabetes CenterThe First Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina
| | - Hai Li
- Department of Endocrinology and Diabetes CenterThe First Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina
| | - Haipeng Xiao
- Department of Endocrinology and Diabetes CenterThe First Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina
| | - Yanbing Li
- Department of Endocrinology and Diabetes CenterThe First Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina
| | - Hongyu Guan
- Department of Endocrinology and Diabetes CenterThe First Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina
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10
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Ren L, Ju F, Liu S, Cai Y, Gang X, Wang G. New Perspectives on Obesity-Associated Nephropathy from Pathophysiology to Therapeutics: Revealing the Promise of GLP-1 RA Therapy. Drug Des Devel Ther 2024; 18:4257-4272. [PMID: 39347536 PMCID: PMC11437658 DOI: 10.2147/dddt.s476815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Accepted: 09/10/2024] [Indexed: 10/01/2024] Open
Abstract
Obesity represents a substantial risk factor for a multitude of metabolic disorders, which seriously threatens human life and health. As the global obesity epidemic intensifies, obesity-related nephropathy (ORN) has attracted great attention. ORN arises from both physical/mechanical and non-physical insults to the glomerular and tubular structures precipitated by obesity, culminating in structural impairments and functional aberrations within the kidneys. Physical injury factors include changes in renal hemodynamics, renal compression, and mechanical stretching of podocytes. Non-physical injury factors include overactivation of the RAAS system, insulin resistance, lipotoxicity, inflammation, and dysregulation of bile acid metabolism. Exploring molecules that target modulation of physical or nonphysical injury factors is a potential approach to ORN treatment. ORN is characterized clinically by microproteinuria and pathologically by glomerulomegaly, which is atypical and makes early diagnosis difficult. Investigating early diagnostic markers for ORN thus emerges as a critical direction for future research. Additionally, there is no specific drug for ORN in clinical treatment, which mainly focuses on weight reduction, mitigating proteinuria, and preserving renal function. In our review, we delineate a progressive therapeutic approach involving enhancements in lifestyle, pharmacotherapy, and bariatric surgery. Our emphasis underscores glucagon-like peptide-1 receptor agonists (GLP-1 RAs) as poised to emerge as pivotal therapeutic modalities for ORN in forthcoming clinical avenues.
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Affiliation(s)
- Linan Ren
- Department of Endocrinology and Metabolism, First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China
- Institute of Translational Medicine, First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China
| | - Feng Ju
- Department of Orthopedics, Yuci District People’s Hospital, Yuci, Shanxi, 030600, People’s Republic of China
| | - Siyuan Liu
- Department of Endocrinology and Metabolism, First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China
- Institute of Translational Medicine, First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China
| | - Yunjia Cai
- Department of Endocrinology and Metabolism, First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China
- Institute of Translational Medicine, First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China
| | - Xiaokun Gang
- Department of Endocrinology and Metabolism, First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China
| | - Guixia Wang
- Department of Endocrinology and Metabolism, First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China
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11
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Mao TH, Huang HQ, Zhang CH. Clinical characteristics and treatment compounds of obesity-related kidney injury. World J Diabetes 2024; 15:1091-1110. [PMID: 38983811 PMCID: PMC11229974 DOI: 10.4239/wjd.v15.i6.1091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Revised: 12/22/2023] [Accepted: 04/08/2024] [Indexed: 06/11/2024] Open
Abstract
Disorders in energy homeostasis can lead to various metabolic diseases, particularly obesity. The obesity epidemic has led to an increased incidence of obesity-related nephropathy (ORN), a distinct entity characterized by proteinuria, glomerulomegaly, progressive glomerulosclerosis, and renal function decline. Obesity and its associated renal damage are common in clinical practice, and their incidence is increasing and attracting great attention. There is a great need to identify safe and effective therapeutic modalities, and therapeutics using chemical compounds and natural products are receiving increasing attention. However, the summary is lacking about the specific effects and mechanisms of action of compounds in the treatment of ORN. In this review, we summarize the important clinical features and compound treatment strategies for obesity and obesity-induced kidney injury. We also summarize the pathologic and clinical features of ORN as well as its pathogenesis and potential therapeutics targeting renal inflammation, oxidative stress, insulin resistance, fibrosis, kidney lipid accumulation, and dysregulated autophagy. In addition, detailed information on natural and synthetic compounds used for the treatment of obesity-related kidney disease is summarized. The synthesis of detailed information aims to contribute to a deeper understanding of the clinical treatment modalities for obesity-related kidney diseases, fostering the anticipation of novel insights in this domain.
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Affiliation(s)
- Tuo-Hua Mao
- Department of Endocrinology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
| | - Han-Qi Huang
- Department of Endocrinology, Hubei No. 3 People’s Hospital of Jianghan University, Wuhan 430033, Hubei Province, China
| | - Chuan-Hai Zhang
- Department of Physiology, UT Southwestern Medical Center, Dallas, TX 75390, United States
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12
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López-Martínez M, Armengol MP, Pey I, Farré X, Rodríguez-Martínez P, Ferrer M, Porrini E, Luis-Lima S, Díaz-Martín L, Rodríguez-Rodríguez AE, Cruz-Perera C, Alcalde M, Navarro-Díaz M. Integrated miRNA-mRNA Analysis Reveals Critical miRNAs and Targets in Diet-Induced Obesity-Related Glomerulopathy. Int J Mol Sci 2024; 25:6437. [PMID: 38928144 PMCID: PMC11204096 DOI: 10.3390/ijms25126437] [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: 05/01/2024] [Revised: 06/02/2024] [Accepted: 06/08/2024] [Indexed: 06/28/2024] Open
Abstract
This study aimed to investigate obesity-related glomerulopathy (ORG) at cellular, structural, and transcriptomic levels. Thirty Wistar rats were randomized into two groups: 15 rats were fed with a standard diet (SD-rats), and 15 rats were fed with a high-fat diet (HFD-rats). After 10 weeks, the weight, kidney function, histological features, and transcriptomic changes were assessed. HFD-rats gained significantly more weight (55.8% vs. 29.2%; p < 0.001) and albuminuria (10,384.04 ng/mL vs. 5845.45 ng/mL; p < 0.001) compared to SD-rats. HFD-rats exhibited early stages of ORG, with predominant mesangial matrix increase and podocyte hypertrophy (PH). These lesions correlated with differentially expressed (DE) genes and miRNAs. Functional analysis showed that miR-205, which was DE in both the kidneys and urine of HFD-rats, negatively regulated the PTEN gene, promoting lipid endocytosis in podocytes. The downregulation of PTEN was proved through a higher PTEN/nephrin ratio in the SD-rats and the presence of lipid vacuoles in HFD-podocytes. This study has found a specific targetome of miRNAs and gene expression in early stages of ORG. Also, it emphasizes the potential value of miR-205 as a urinary biomarker for detecting podocyte injury in ORG, offering a tool for early diagnosis, and opening new avenues for future therapeutic research of obesity-related glomerulopathy.
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Affiliation(s)
- Marina López-Martínez
- CSUR National Unit of Expertise for Complex Glomerular Diseases of Spain, Nephrology Department, Vall d’Hebron University Hospital, Vall d’Hebron Institute of Research, 08035 Barcelona, Spain
- Department of Medicine, Universitat Autònoma de Barcelona, Bellaterra, 08913 Barcelona, Spain
| | - Maria Pilar Armengol
- Genomic Platform, Germans Trias i Pujol’s Research Institute, Badalona, 08916 Barcelona, Spain
| | - Irina Pey
- Genomic Platform, Germans Trias i Pujol’s Research Institute, Badalona, 08916 Barcelona, Spain
| | - Xavier Farré
- Genomic Platform, Germans Trias i Pujol’s Research Institute, Badalona, 08916 Barcelona, Spain
| | | | - Mireia Ferrer
- Statistics and Bioinformatics Unit, Vall d’Hebron Research Institute, 08035 Barcelona, Spain
| | - Esteban Porrini
- Laboratory of Renal Function (LFR), Faculty of Medicine, University of La Laguna, Complejo Hospitalario Universitario de Canarias, 38320 La Laguna, Spain (L.D.-M.)
- Instituto de Tecnologías Biomédicas (ITB), Faculty of Medicine, University of La Laguna, La Laguna, 38320 Tenerife, Spain
| | - Sergio Luis-Lima
- Laboratory of Renal Function (LFR), Faculty of Medicine, University of La Laguna, Complejo Hospitalario Universitario de Canarias, 38320 La Laguna, Spain (L.D.-M.)
- Department of Laboratory Medicine, Complejo Hospitalario Universitario de Canarias, La Laguna, 38320 Tenerife, Spain
| | - Laura Díaz-Martín
- Laboratory of Renal Function (LFR), Faculty of Medicine, University of La Laguna, Complejo Hospitalario Universitario de Canarias, 38320 La Laguna, Spain (L.D.-M.)
| | - Ana Elena Rodríguez-Rodríguez
- Research Unit, Hospital Universitario de Canarias, La Laguna, 38320 Tenerife, Spain
- Fundación General de la Universidad, University of La Laguna,38320 Tenerife, Spain
| | - Coriolano Cruz-Perera
- Laboratory of Renal Function (LFR), Faculty of Medicine, University of La Laguna, Complejo Hospitalario Universitario de Canarias, 38320 La Laguna, Spain (L.D.-M.)
| | - Marta Alcalde
- Comparative Medicine and Bioimage Centre of Catalonia (CMCiB), Fundació Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, 08916 Barcelona, Spain
- Pharmaco and Device Epidemiology Group, CSM, NDORMS, University of Oxford, Oxford OX1 3PT, UK
| | - Maruja Navarro-Díaz
- Genomic Platform, Germans Trias i Pujol’s Research Institute, Badalona, 08916 Barcelona, Spain
- Nephrology Department, Sant Joan Despí Moisès Broggi Hospital, Sant Joan Despí, 08970 Barcelona, Spain
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Yau K, Kuah R, Cherney DZI, Lam TKT. Obesity and the kidney: mechanistic links and therapeutic advances. Nat Rev Endocrinol 2024; 20:321-335. [PMID: 38351406 DOI: 10.1038/s41574-024-00951-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/02/2024] [Indexed: 02/19/2024]
Abstract
Obesity is strongly associated with the development of diabetes mellitus and chronic kidney disease (CKD), but there is evidence for a bidirectional relationship wherein the kidney also acts as a key regulator of body weight. In this Review, we highlight the mechanisms implicated in obesity-related CKD, and outline how the kidney might modulate feeding and body weight through a growth differentiation factor 15-dependent kidney-brain axis. The favourable effects of bariatric surgery on kidney function are discussed, and medical therapies designed for the treatment of diabetes mellitus that lower body weight and preserve kidney function independent of glycaemic lowering, including sodium-glucose cotransporter 2 inhibitors, incretin-based therapies and metformin, are also reviewed. In summary, we propose that kidney function and body weight are related in a bidirectional fashion, and that this interrelationship affects human health and disease.
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Affiliation(s)
- Kevin Yau
- Division of Nephrology, Department of Medicine, Toronto General Hospital, Toronto, Ontario, Canada
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Rachel Kuah
- Department of Physiology, University of Toronto, Toronto, Ontario, Canada
- Toronto General Hospital Research Institute, UHN, Toronto, Ontario, Canada
| | - David Z I Cherney
- Division of Nephrology, Department of Medicine, Toronto General Hospital, Toronto, Ontario, Canada.
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
- Toronto General Hospital Research Institute, UHN, Toronto, Ontario, Canada.
| | - Tony K T Lam
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
- Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
- Toronto General Hospital Research Institute, UHN, Toronto, Ontario, Canada.
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14
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Ali MM, Parveen S, Williams V, Dons R, Uwaifo GI. Cardiometabolic comorbidities and complications of obesity and chronic kidney disease (CKD). J Clin Transl Endocrinol 2024; 36:100341. [PMID: 38616864 PMCID: PMC11015524 DOI: 10.1016/j.jcte.2024.100341] [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] [Received: 02/08/2024] [Revised: 03/28/2024] [Accepted: 03/29/2024] [Indexed: 04/16/2024] Open
Abstract
Obesity and chronic kidney disease are two ongoing progressive clinical pandemics of major public health and clinical care significance. Because of their growing prevalence, chronic indolent course and consequent complications both these conditions place significant burden on the health care delivery system especially in developed countries like the United States. Beyond the chance coexistence of both of these conditions in the same patient based on high prevalence it is now apparent that obesity is associated with and likely has a direct causal role in the onset, progression and severity of chronic kidney disease. The causes and underlying pathophysiology of this are myriad, complicated and multi-faceted. In this review, continuing the theme of this special edition of the journal on " The Cross roads between Endocrinology and Nephrology" we review the epidemiology of obesity related chronic kidney disease (ORCKD), and its various underlying causes and pathophysiology. In addition, we delve into the consequent comorbidities and complications associated with ORCKD with particular emphasis on the cardio metabolic consequences and then review the current body of evidence for available strategies for chronic kidney disease modulation in ORCKD as well as the potential unique role of weight reduction and management strategies in its improvement and risk reduction.
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Affiliation(s)
- Mariam M. Ali
- Southern Illinois School of Medicine, Department of Medicine, Section of Endocrinology, Diabetes and Metabolism, 751 North Rutledge Street, Moy Building, Suite 1700, Springfield, Il 62702, United States
| | - Sanober Parveen
- Southern Illinois School of Medicine, Department of Medicine, Section of Endocrinology, Diabetes and Metabolism, 751 North Rutledge Street, Moy Building, Suite 1700, Springfield, Il 62702, United States
| | - Vanessa Williams
- Southern Illinois School of Medicine, Department of Medicine, Section of Endocrinology, Diabetes and Metabolism, 751 North Rutledge Street, Moy Building, Suite 1700, Springfield, Il 62702, United States
| | - Robert Dons
- Southern Illinois School of Medicine, Department of Medicine, Section of Endocrinology, Diabetes and Metabolism, 751 North Rutledge Street, Moy Building, Suite 1700, Springfield, Il 62702, United States
| | - Gabriel I. Uwaifo
- Section of Endocrinology, Dept of Medicine, SIU School of Medicine, 751 N Rutledge St, Moy Building, Suite 1700, Room #1813, Springfield, Il 62702, United States
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Hao M, Lv Y, Liu S, Guo W. The New Challenge of Obesity - Obesity-Associated Nephropathy. Diabetes Metab Syndr Obes 2024; 17:1957-1971. [PMID: 38737387 PMCID: PMC11086398 DOI: 10.2147/dmso.s433649] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Accepted: 02/28/2024] [Indexed: 05/14/2024] Open
Abstract
In recent years, obesity has become one of the major diseases that affect human health and consume human health resources, especially when it causes comorbidities such as hypertension, diabetes, cardiovascular disease and kidney disease. Many studies have demonstrated that obesity is associated with the development of chronic kidney disease and can exacerbate the progression of end-stage renal disease. This review described the mechanisms associated with the development of obesity-associated nephropathy and the current relevant therapeutic modalities, with the aim of finding new therapeutic targets for obesity-associated nephropathy. The mechanisms of obesity-induced renal injury include, in addition to the traditional alterations in renal hemodynamics, the involvement of various mechanisms such as macrophage infiltration in adipose tissue, alterations in adipokines (leptin and adiponectin), and ectopic deposition of lipids. At present, there is no "point-to-point" treatment for obesity-induced kidney injury. The renin-angiotensin-aldosterone system (RAAS) inhibitors, sodium-dependent glucose transporter 2 (SGLT-2) inhibitors and bariatric surgery described in this review can reduce urinary protein to varying degrees and delay the progression of kidney disease. In addition, recent studies on the therapeutic effects of intestinal flora on obesity may reduce the incidence of obesity-related kidney disease from the perspective of primary prevention. Both of these interventions have their own advantages and disadvantages, so the continuous search for the mechanism of obesity-induced related kidney disease will be extremely helpful for the future treatment of obesity-related kidney disease.
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Affiliation(s)
- Mengjin Hao
- Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China
- Department of Endocrinology, Jining No. 1 People’s Hospital, Jining, Shandong, 272000, People’s Republic of China
| | - You Lv
- Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China
| | - Siyuan Liu
- Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China
| | - Weiying Guo
- Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China
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Lu T, Kan J, He X, Zou J, Sheng D, Xue Y, Wang Y, Xu L. Gastric Submucosal Fat Accumulation Is Associated with Insulin Resistance in Patients with Obesity. Obes Surg 2024; 34:534-541. [PMID: 38191965 PMCID: PMC10811089 DOI: 10.1007/s11695-023-07014-2] [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: 07/25/2023] [Revised: 12/14/2023] [Accepted: 12/15/2023] [Indexed: 01/10/2024]
Abstract
PURPOSE Ectopic fat accumulation plays a significant role in obesity-related metabolic dysfunction, and few studies have reported an association between ectopic gastric fat and metabolic risk factors. We aim to fulfill this need by assessing the degree of gastric submucosal fat accumulation in pathologic sections of 190 sleeve gastrectomy specimens. METHODS Study patients were divided into two groups (D1 and D2) based on whether fat accumulation exceeded 1/3 of the submucosa of the stomach. Demographic and metabolic risk factors were compared between the two groups. Metabolic risk variables that might be associated with the degree of fat accumulation were screened in the original cohort. After balancing for possible confounders, the robustness of the correlations was assessed using binary and conditional logistic regression analyses. RESULTS All study patients had fat accumulation in the submucosa of the stomach. C-reactive protein (CRP), body mass index (BMI), visceral fat area (VFA), and insulin resistance (IR) were higher in the D2 group than in the D1 group in the original cohort (P < 0.05). Logistic regression analysis showed that BMI and IR may be associated with increased fat accumulation. After balancing variables other than obesity indicators and IR using propensity score matching, BMI and IR remained significantly different between the two groups (P < 0.05). Further analysis of the matched cohort using two logistic regression analyses showed that IR was an independent risk factor for increased fat accumulation. CONCLUSION This study indicated that gastric submucosal fat accumulation was prevalent in patients with obesity and was associated with IR.
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Affiliation(s)
- Tao Lu
- Department of General Surgery, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan Road, Nanjing, 210011, Jiangsu Province, China
| | - Jianxun Kan
- Department of General Surgery, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan Road, Nanjing, 210011, Jiangsu Province, China
| | - Xue He
- Department of Pathology, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan Road, Nanjing, 210011, Jiangsu Province, China
| | - Jialai Zou
- Department of General Surgery, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan Road, Nanjing, 210011, Jiangsu Province, China
| | - Dandan Sheng
- Department of Nuclear Medicine, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan Road, Nanjing, 210011, Jiangsu Province, China
| | - Yating Xue
- Department of Pathology, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan Road, Nanjing, 210011, Jiangsu Province, China
| | - Yan Wang
- Department of Pathology, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan Road, Nanjing, 210011, Jiangsu Province, China
| | - Lijian Xu
- Department of General Surgery, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan Road, Nanjing, 210011, Jiangsu Province, China.
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17
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Chen X, Xiang J, Gao P, Wang L, Xiang L, Lu Z, Cao T, Mou A, Zhang X, Jiang X, Zhu Z, Lang H. Artemisinin alleviates obesity-related glomerulopathy by downregulating CYP24A1 expression. Diabetes Obes Metab 2024; 26:767-771. [PMID: 37921082 DOI: 10.1111/dom.15355] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Revised: 10/16/2023] [Accepted: 10/18/2023] [Indexed: 11/04/2023]
Affiliation(s)
- Xiaorong Chen
- Medical College, Southwest Jiaotong University, Chengdu, China
- Department of General Medicine, Chengdu Second People's Hospital, Chengdu, China
| | - Jie Xiang
- Medical College, Southwest Jiaotong University, Chengdu, China
- Department of General Medicine, Chengdu Second People's Hospital, Chengdu, China
| | - Peng Gao
- Department of Hypertension and Endocrinology, Centre for Hypertension and Metabolic Diseases, Daping Hospital, Army Medical University, and Chongqing Institute of Hypertension, Chongqing, China
| | - Lijuan Wang
- Department of Hypertension and Endocrinology, Centre for Hypertension and Metabolic Diseases, Daping Hospital, Army Medical University, and Chongqing Institute of Hypertension, Chongqing, China
| | - Li Xiang
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
| | - Zongshi Lu
- Department of Hypertension and Endocrinology, Centre for Hypertension and Metabolic Diseases, Daping Hospital, Army Medical University, and Chongqing Institute of Hypertension, Chongqing, China
| | - Tingbing Cao
- Department of Hypertension and Endocrinology, Centre for Hypertension and Metabolic Diseases, Daping Hospital, Army Medical University, and Chongqing Institute of Hypertension, Chongqing, China
| | - Aidi Mou
- Department of Hypertension and Endocrinology, Centre for Hypertension and Metabolic Diseases, Daping Hospital, Army Medical University, and Chongqing Institute of Hypertension, Chongqing, China
| | - Xingping Zhang
- Department of General Medicine, Chengdu Second People's Hospital, Chengdu, China
| | - Xiaoyan Jiang
- Department of Endocrinology and Metabolism, Chongqing Emergency Medical Centre, Chongqing University Central Hospital, Chongqing, China
| | - Zhiming Zhu
- Department of Hypertension and Endocrinology, Centre for Hypertension and Metabolic Diseases, Daping Hospital, Army Medical University, and Chongqing Institute of Hypertension, Chongqing, China
| | - Hongmei Lang
- Department of General Medicine, Chengdu Second People's Hospital, Chengdu, China
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18
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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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Abstract
PURPOSE OF REVIEW Chronic kidney disease (CKD) is a common condition and a major cause of morbidity and mortality in adults, but children and adolescents are also at risk for early kidney injury and development of CKD. Obesity contributes both directly and indirectly to the development of CKD. The purpose of this review is to describe obesity-related kidney disease (ORKD) and diabetic kidney disease (DKD) and their impact in the pediatric population. RECENT FINDINGS Although obesity-related CKD in childhood and adolescence is uncommon, nascent kidney damage may magnify the lifetime risk of CKD. Glomerular hyperfiltration is an early phenotype of both ORKD and DKD and typically manifests prior to albuminuria and progressive decline in GFR. Novel treatments for obesity and type 2 diabetes exerting protective effects on the kidneys are being investigated for use in the pediatric population. It is important to understand the impact of obesity on the kidneys more fully in the pediatric population to help detect injury earlier and intervene prior to the onset of irreversible progression of disease and to guide future research in this area.
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Affiliation(s)
- Alexandra Sawyer
- Department of Pediatrics, Division of Endocrinology, University of Colorado School of Medicine, 13123 East 16Th Avenue, Box 158, Aurora, CO, 80045, USA.
| | - Evan Zeitler
- Department of Medicine, Division of Nephrology and Hypertension, University of North Carolina Kidney Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Howard Trachtman
- Department of Pediatrics, Division of Nephrology, University of Michigan, Ann Arbor, MI, USA
| | - Petter Bjornstad
- Department of Pediatrics, Division of Endocrinology, University of Colorado School of Medicine, 13123 East 16Th Avenue, Box 158, Aurora, CO, 80045, USA
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20
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Kataoka H, Nitta K, Hoshino J. Glomerular hyperfiltration and hypertrophy: an evaluation of maximum values in pathological indicators to discriminate "diseased" from "normal". Front Med (Lausanne) 2023; 10:1179834. [PMID: 37521339 PMCID: PMC10372422 DOI: 10.3389/fmed.2023.1179834] [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: 03/05/2023] [Accepted: 06/05/2023] [Indexed: 08/01/2023] Open
Abstract
The success of sodium-glucose cotransporter 2 inhibitors and bariatric surgery in patients with chronic kidney disease has highlighted the importance of glomerular hyperfiltration and hypertrophy in the progression of kidney disease. Sustained glomerular hyperfiltration and hypertrophy can lead to glomerular injury and progressive kidney damage. This article explores the relationship between obesity and chronic kidney disease, focusing on the roles of glomerular hyperfiltration and hypertrophy as hallmarks of obesity-related kidney disease. The pathological mechanisms underlying this association include adipose tissue inflammation, dyslipidemia, insulin resistance, chronic systemic inflammation, oxidative stress, and overactivation of the sympathetic nervous system, as well as the renin-angiotensin aldosterone system. This article explains how glomerular hyperfiltration results from increased renal blood flow and intraglomerular hypertension, inducing mechanical stress on the filtration barrier and post-filtration structures. Injured glomeruli increase in size before sclerosing and collapsing. Therefore, using extreme values, such as the maximal glomerular diameter, could improve the understanding of the data distribution and allow for better kidney failure predictions. This review provides important insights into the mechanisms underlying glomerular hyperfiltration and hypertrophy and highlights the need for further research using glomerular size, including maximum glomerular profile, calculated using needle biopsy specimens.
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Yang Y, Yu J, Huo J, Yan Y. Sesamolin Attenuates Kidney Injury, Intestinal Barrier Dysfunction, and Gut Microbiota Imbalance in High-Fat and High-Fructose Diet-Fed Mice. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2023; 71:1562-1576. [PMID: 36630317 DOI: 10.1021/acs.jafc.2c07084] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/17/2023]
Abstract
This study investigated the effects of sesamolin on kidney injury, intestinal barrier dysfunction, and gut microbiota imbalance in high-fat and high-fructose (HF-HF) diet-fed mice and explored the underlying correlations among them. The results indicated that sesamolin suppressed metabolic disorders and increased renal function parameters. Histological evaluation showed that sesamolin mitigated renal epithelial cell degeneration and brush border damage. Meanwhile, sesamolin inhibited the endotoxin-mediated induction of the Toll-like receptor 4-related IKKα/NF-κB p65 pathway activation. Additionally, sesamolin mitigated intestinal barrier dysfunction and improved the composition of gut microbiota. The correlation results further indicated that changes in the dominant phyla, including Firmicutes, Deferribacterota, Desulfobacterota, and Bacteroidota, were more highly correlated with a reduction in endotoxemia and metabolic disorders, as well as decreases in intestinal proinflammatory response and related renal risk biomarkers. The results of this study suggest that sesamolin attenuates kidney injuries, which might be associated with its effects on the reduction of endotoxemia and related metabolic disorders through the restoration of the intestinal barrier and the modulation of gut microbiota. Thus, sesamolin may be a potential dietary supplement for protection against obesity-associated kidney injury.
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Affiliation(s)
- Yang Yang
- Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi'an 710119, China
| | - Jing Yu
- Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi'an 710119, China
| | - Jiayao Huo
- Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi'an 710119, China
| | - Yaping Yan
- Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi'an 710119, China
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22
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Kataoka H, Nitta K, Hoshino J. Visceral fat and attribute-based medicine in chronic kidney disease. Front Endocrinol (Lausanne) 2023; 14:1097596. [PMID: 36843595 PMCID: PMC9947142 DOI: 10.3389/fendo.2023.1097596] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Accepted: 01/13/2023] [Indexed: 02/11/2023] Open
Abstract
Visceral adipose tissue plays a central role in obesity and metabolic syndrome and is an independent risk factor for both cardiovascular and metabolic disorders. Increased visceral adipose tissue promotes adipokine dysregulation and insulin resistance, leading to several health issues, including systemic inflammation, oxidative stress, and activation of the renin-angiotensin-aldosterone system. Moreover, an increase in adipose tissue directly and indirectly affects the kidneys by increasing renal sodium reabsorption, causing glomerular hyperfiltration and hypertrophy, which leads to increased proteinuria and kidney fibrosis/dysfunction. Although the interest in the adverse effects of obesity on renal diseases has grown exponentially in recent years, the relationship between obesity and renal prognosis remains controversial. This may be attributed to the long clinical course of obesity, numerous obesity-related metabolic complications, and patients' attributes. Multiple individual attributes influencing the pathophysiology of fat accumulation make it difficult to understand obesity. In such cases, it may be effective to elucidate the pathophysiology by conducting research tailored to individual attributes from the perspective of attribute-based medicine/personalized medicine. We consider the appropriate use of clinical indicators necessary, according to attributes such as chronic kidney disease stage, level of visceral adipose tissue accumulation, age, and sex. Selecting treatments and clinical indicators based on individual attributes will allow for advancements in the clinical management of patients with obesity and chronic kidney disease. In the clinical setting of obesity-related nephropathy, it is first necessary to accumulate attribute-based studies resulting from the accurate evaluation of visceral fat accumulation to establish evidence for promoting personalized medicine.
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Abstract
The prevalence of obesity has increased dramatically during the past decades, which has been a major health problem. Since 1975, the number of people with obesity worldwide has nearly tripled. An increasing number of studies find obesity as a driver of chronic kidney disease (CKD) progression, and the mechanisms are complex and include hemodynamic changes, inflammation, oxidative stress, and activation of the renin-angiotensin-aldosterone system (RAAS). Obesity-related kidney disease is characterized by glomerulomegaly, which is often accompanied by localized and segmental glomerulosclerosis lesions. In these patients, the early symptoms are atypical, with microproteinuria being the main clinical manifestation and nephrotic syndrome being rare. Weight loss and RAAS blockers have a protective effect on obesity-related CKD, but even so, a significant proportion of patients eventually progress to end-stage renal disease despite treatment. Thus, it is critical to comprehend the mechanisms underlying obesity-related CKD to create new tactics for slowing or stopping disease progression. In this review, we summarize current knowledge on the mechanisms of obesity-related kidney disease, its pathological changes, and future perspectives on its treatment.
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Affiliation(s)
- Zongmiao Jiang
- Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, China
| | - Yao Wang
- Department of Orthopedics, The Second Hospital Jilin University, Changchun, China
| | - Xue Zhao
- Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, China
| | - Haiying Cui
- Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, China
| | - Mingyue Han
- Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, China
| | - Xinhua Ren
- Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, China
| | - Xiaokun Gang
- Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, China
| | - Guixia Wang
- Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, China
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Pacholewicz J, Kuligowska E, Szylińska A, Walerowicz P, Biskupski A, Sielicki P, Kotfis K, Listewnik M. The Rate of Postoperative Mortality and Renal and Respiratory Complications are Increased in Patients with Extreme Obesity Undergoing Cardiac Surgery - A Retrospective Observational Cohort Study of 8848 Patients. Diabetes Metab Syndr Obes 2023; 16:1155-1166. [PMID: 37122675 PMCID: PMC10145505 DOI: 10.2147/dmso.s400597] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Accepted: 04/10/2023] [Indexed: 05/02/2023] Open
Abstract
Introduction The importance of obesity as a potential risk factor in open heart surgery is well known. The epidemic of extreme obesity is an increasing public health concern and raises alerts regarding postoperative complications and mortality in patients undergoing cardiac surgery. The study aimed to analyze the impact of extreme obesity (BMI≥40) on the frequency of postoperative complications, as well as early and delayed mortality compared to patients with a lower body mass. Materials and Methodology This retrospective observational cohort study involved patients, over the age of 18, undergoing cardiac surgery with cardiopulmonary bypass at the Cardiac Surgery Department of the Pomeranian Medical University in Szczecin, Poland between January 1st, 2010 and December 31st, 2018. The patients included in the study were allocated into two subgroups depending on the BMI index (Group I BMI≥40 vs Group II BMI<40). Results A total of 8848 adult patients of both genders were included. Baseline characteristics for Group I and Group II were mean age 64.07±7.76 vs 65.10±9.68 years (p=0.123), mean BMI 42.13±2.44 vs 28.55±4.23 (p<0.001), with more females in Group I (58.04% vs 29.06%) and more males in Group II (70.94% vs 29.06%), p<0.001. The predicted perioperative risk using the EuroScore Logistics scale was higher in a group with BMI≥40 (p<0.001). Regression analysis with adjustment for confounding factors showed a statistically significant relationship between BMI≥40 and postoperative respiratory failure (OR=1.760, p=0.043), acute kidney injury AKIN2 (OR=2.082, p=0.044) and AKIN3 (OR=2.743, p=0.039). 30-day mortality in the univariate analysis showed a statistically significant relationship, however, after modifying the results with interfering factors, no statistical significance was obtained. Conclusion The risk of postoperative acute respiratory failure and acute renal injury was increased in patients with BMI≥40. The probability of 30-day survival of patients after cardiac surgery was much lower in people with extreme obesity, although it was related to the dominant comorbidities. The 10-year survival was comparable in both groups.
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Affiliation(s)
- Jerzy Pacholewicz
- Department of Cardiac Surgery, Pomeranian Medical University, Szczecin, Poland
| | - Ewelina Kuligowska
- Department of Cardiac Surgery, Pomeranian Medical University, Szczecin, Poland
| | - Aleksandra Szylińska
- Department of Medical Rehabilitation and Clinical Physiotherapy, Pomeranian Medical University, Szczecin, Poland
| | - Paweł Walerowicz
- Department of Cardiac Surgery, Pomeranian Medical University, Szczecin, Poland
| | - Andrzej Biskupski
- Department of Cardiac Surgery, Pomeranian Medical University, Szczecin, Poland
| | - Piotr Sielicki
- Department of Cardiac Surgery, Pomeranian Medical University, Szczecin, Poland
| | - Katarzyna Kotfis
- Department of Anesthesiology, Intensive Therapy and Acute Intoxications, Pomeranian Medical University, Szczecin, Poland
- Correspondence: Katarzyna Kotfis, Department of Anesthesiology, Intensive Therapy and Acute Intoxications, Pomeranian Medical University, Szczecin, Poland, Email
| | - Mariusz Listewnik
- Department of Cardiac Surgery, Pomeranian Medical University, Szczecin, Poland
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25
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Mohammed RA, Danda AK, Kotakadi SM, Nannepaga JS. Anti-obesity Effect of Bioengineered Silver Nanoparticles Synthesized from Persea americana on Obese Albino Rats. Pharm Nanotechnol 2023; 11:433-446. [PMID: 37106516 DOI: 10.2174/2211738511666230427145944] [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: 09/29/2022] [Revised: 12/28/2022] [Accepted: 01/09/2023] [Indexed: 04/29/2023]
Abstract
BACKGROUND Obesity is an immoderate or abnormal accretion of fat or adipose tissue in the body that is prone to damage the health of mankind. Persea americana (Avocados) is a nutritious fruit known for its several health benefits. The current research was planned to evaluate the anti-obesity activity of bioengineered Silver Nanoparticles (AgNPs) against a high-fat diet (HFD) treated obese albino rats. METHODS AgNPs were synthesized and characterized for the Phytochemical constituents, UV-vis Spectroscopy, FTIR, SEM and XRD. Furthermore, the lipid profile in serum, biochemical parameters and histopathological changes in tissues of albino rats were determined. RESULTS The present study revealed the presence of tannins, flavonoids, steroids and saponins, carbohydrates, alkaloids, phenols and glycosides. The peak was disclosed at 402 nm in UV-vis spectroscopy, confirming the synthesis of AgNPs. FTIR analysis showed two peaks at 3332.25 cm-1 which correspond to the O-H stretch of the carboxylic acid band, and 1636.40 cm-1 represents the N-H stretch of the amide of proteins, respectively. This result confirms their contribution to the capping and stabilization of AgNPs. The XRD results confirm the crystalline nature of AgNPs, and SEM results indicated that the synthesized AgNPs were spherical. Further, the results of the current study showed the improved lipid profile and biochemical parameters in rats supplemented with methanolic pulp extract of Persea americana AgNPs when compared with other experimental groups. The histopathological findings displayed improved results with reduced hepatocyte degradation under the influence of AgNPs treatment. CONCLUSION All the experimental evidence indicated the possible anti-obesity effect of silver nanoparticles synthesized from the methanolic pulp extract of Persea americana.
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Affiliation(s)
- Reshma Anjum Mohammed
- Department of Biotechnology, Sri Padmavati Mahila Visvavidyalayam (Women's University), Tirupati, 517 502, Andhra, India
| | - Aruna Kumari Danda
- Department of Zoology, Government Degree College, Anantapur, 515001, Andhra Pradesh, India
| | - Sai Manogna Kotakadi
- Department of Biotechnology, Sri Padmavati Mahila Visvavidyalayam (Women's University), Tirupati, 517 502, Andhra, India
| | - John Sushma Nannepaga
- Department of Biotechnology, Sri Padmavati Mahila Visvavidyalayam (Women's University), Tirupati, 517 502, Andhra, India
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26
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van Dam MJCM, Pottel H, Vreugdenhil ACE. Relation between obesity-related comorbidities and kidney function estimation in children. Pediatr Nephrol 2022; 38:1867-1876. [PMID: 36416955 PMCID: PMC10154263 DOI: 10.1007/s00467-022-05810-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Revised: 10/28/2022] [Accepted: 10/28/2022] [Indexed: 11/24/2022]
Abstract
BACKGROUND The current childhood obesity pandemic is likely to result in an increased risk of chronic kidney disease (CKD) later in life. Correlations between obesity-related comorbidities and kidney function can be found, but it is unclear to what extent this is caused by bias due to different mathematical forms of the estimated glomerular filtration rate (eGFR) equations. The present study aimed to analyze correlations between obesity-related comorbidities and different eGFR equations and to investigate whether rescaled serum creatinine (SCr/Q) for sex and age or height might be an alternative biomarker for kidney function estimation. METHODS This cross-sectional cohort study included 600 children with overweight and obesity. Mean age was 12.20 ± 3.28 years, 53.5% were female, and mean BMI z-score was 3.31 ± 0.75. All children underwent a comprehensive assessment that included anthropometrical and blood pressure measurements, laboratory examination, air displacement plethysmography, and polysomnography. Qage and Qheight polynomials were used to rescale SCr and multiple creatinine-based eGFR equations were compared. RESULTS SCr/Q and almost all GFR estimations significantly correlated with a waist-to-hip ratio, fat mass, homeostasis model assessment for insulin resistance, and triacylglyceride, HDL cholesterol, alanine transaminase, and serum uric acid concentrations. Multiple correlations, however, were not confirmed by all equations, which suggests dependency on the mathematical form of the different eGFR equations. CONCLUSIONS Correlations between obesity-related comorbidities and creatinine-based eGFR are present in children with overweight and obesity, but depend to a large extent on the eGFR equation of choice. SCr/Q might be an alternative biomarker for assessing correlations between obesity-related comorbidities and kidney function in children with overweight and obesity. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Affiliation(s)
- Mark J C M van Dam
- Centre for Overweight Adolescent and Children's Healthcare (COACH), Department of Pediatrics, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Centre +, Maastricht, The Netherlands.
| | - Hans Pottel
- Department of Public Health and Primary Care, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium
| | - Anita C E Vreugdenhil
- Centre for Overweight Adolescent and Children's Healthcare (COACH), Department of Pediatrics, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Centre +, Maastricht, The Netherlands
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27
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Martínez-Montoro JI, Morales E, Cornejo-Pareja I, Tinahones FJ, Fernández-García JC. Obesity-related glomerulopathy: Current approaches and future perspectives. Obes Rev 2022; 23:e13450. [PMID: 35362662 PMCID: PMC9286698 DOI: 10.1111/obr.13450] [Citation(s) in RCA: 50] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Revised: 03/08/2022] [Accepted: 03/09/2022] [Indexed: 12/20/2022]
Abstract
Obesity-related glomerulopathy (ORG) is a silent comorbidity which is increasing in incidence as the obesity epidemic escalates. ORG is associated with serious health consequences including chronic kidney disease, end-stage renal disease (ESRD), and increased mortality. Although the pathogenic mechanisms involved in the development of ORG are not fully understood, glomerular hemodynamic changes, renin-angiotensin-aldosterone system (RAAS) overactivation, insulin-resistance, inflammation and ectopic lipid accumulation seem to play a major role. Despite albuminuria being commonly used for the non-invasive evaluation of ORG, promising biomarkers of early kidney injury that are emerging, as well as new approaches with proteomics and metabolomics, might permit an earlier diagnosis of this disease. In addition, the assessment of ectopic kidney fat by renal imaging could be a useful tool to detect and evaluate the progression of ORG. Weight loss interventions appear to be effective in ORG, although large-scale trials are needed. RAAS blockade has a renoprotective effect in patients with ORG, but even so, a significant proportion of patients with ORG will eventually progress to ESRD despite therapeutic efforts. It is noteworthy that certain antidiabetic agents such as sodium-glucose cotransporter 2 inhibitors (SGLT2i) or glucagon-like peptide-1 receptor agonists (GLP-1 RAs) could be useful in the treatment of ORG through different pleiotropic effects. In this article, we review current approaches and future perspectives in the care and treatment of ORG.
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Affiliation(s)
- José Ignacio Martínez-Montoro
- Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Málaga, Spain.,Faculty of Medicine, University of Málaga, Málaga, Spain.,Instituto de Investigación Biomédica de Málaga-IBIMA, Málaga, Spain
| | - Enrique Morales
- Department of Nephrology, 12 de Octubre University Hospital, Madrid, Spain.,Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain.,Department of Medicine, Complutense University, Madrid, Spain
| | - Isabel Cornejo-Pareja
- Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Málaga, Spain.,Faculty of Medicine, University of Málaga, Málaga, Spain.,Instituto de Investigación Biomédica de Málaga-IBIMA, Málaga, Spain.,Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y la Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain
| | - Francisco J Tinahones
- Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Málaga, Spain.,Faculty of Medicine, University of Málaga, Málaga, Spain.,Instituto de Investigación Biomédica de Málaga-IBIMA, Málaga, Spain.,Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y la Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain
| | - José Carlos Fernández-García
- Faculty of Medicine, University of Málaga, Málaga, Spain.,Instituto de Investigación Biomédica de Málaga-IBIMA, Málaga, Spain.,Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y la Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain.,Department of Endocrinology and Nutrition, Regional University Hospital of Málaga, Málaga, Spain
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28
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Zeitler EM, Jennette JC, Flythe JE, Falk RJ, Poulton JS. High-calorie diet results in reversible obesity-related glomerulopathy in adult zebrafish regardless of dietary fat. Am J Physiol Renal Physiol 2022; 322:F527-F539. [PMID: 35224994 PMCID: PMC8977181 DOI: 10.1152/ajprenal.00018.2022] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Revised: 02/10/2022] [Accepted: 02/22/2022] [Indexed: 11/22/2022] Open
Abstract
Obesity is a risk factor for the development of kidney disease. The role of diet in this association remains undetermined, in part due to practical limitations in studying nutrition in humans. In particular, the relative importance of calorie excess versus dietary macronutrient content is poorly understood. For example, it is unknown if calorie restriction modulates obesity-related kidney pathology. To study the effects of diet-induced obesity in a novel animal model, we treated zebrafish for 8 wk with diets varied in both calorie and fat content. Kidneys were evaluated by light and electron microscopy. We evaluated glomerular filtration barrier function using a dextran permeability assay. We assessed the effect of diet on podocyte sensitivity to injury using an inducible podocyte injury model. We then tested the effect of calorie restriction on the defects caused by diet-induced obesity. Fish fed a high-calorie diet developed glomerulomegaly (mean: 1,211 vs. 1,010 µm2 in controls, P = 0.007), lower podocyte density, foot process effacement, glomerular basement membrane thickening, tubular enlargement (mean: 1,038 vs. 717 µm2 in controls, P < 0.0001), and ectopic lipid deposition. Glomerular filtration barrier dysfunction and increased susceptibility to podocyte injury were observed with high-calorie feeding regardless of dietary fat content. These pathological changes resolved with 4 wk of calorie restriction. Our findings suggest that calorie excess rather than dietary fat drives obesity-related kidney dysfunction and that inadequate podocyte proliferation in response to glomerular enlargement may cause podocyte dysfunction. We also demonstrate the value of zebrafish as a novel model for studying diet in obesity-related kidney disease.NEW & NOTEWORTHY Obesity is a risk factor for kidney disease. The role of diet in this association is difficult to study in humans. In this study, zebrafish fed a high-calorie diet, regardless of fat macronutrient composition, developed glomerulomegaly, foot process effacement, and filtration barrier dysfunction, recapitulating the changes seen in humans with obesity. Calorie restriction reversed the changes. This work suggests that macronutrient composition may be less important than total calories in the development of obesity-related kidney disease.
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Affiliation(s)
- Evan M Zeitler
- Division of Nephrology and Hypertension, Department of Medicine, UNC Kidney Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - J Charles Jennette
- Division of Nephrology and Hypertension, Department of Medicine, UNC Kidney Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
- Nephropathology Division, Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Jennifer E Flythe
- Division of Nephrology and Hypertension, Department of Medicine, UNC Kidney Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Ronald J Falk
- Division of Nephrology and Hypertension, Department of Medicine, UNC Kidney Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - John S Poulton
- Division of Nephrology and Hypertension, Department of Medicine, UNC Kidney Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
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29
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Tibrewala A, Khush KK, Cherikh WS, Foutz J, Stehlik J, Rich JD. Risk of Renal Dysfunction Following Heart Transplantation in Patients Bridged with a Left Ventricular Assist Device. ASAIO J 2022; 68:646-653. [PMID: 34419984 DOI: 10.1097/mat.0000000000001558] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Acute renal failure (ARF) and chronic kidney disease (CKD) are associated with short- and long-term morbidity and mortality following heart transplantation (HT). We investigated the incidence and risk factors for developing ARF requiring hemodialysis (HD) and CKD following HT specifically in patients with a left ventricular assist device (LVAD). We examined the International Society for Heart and Lung Transplantation (ISHLT) Thoracic Transplant Registry for heart transplant patients between January 2000 and June 2015. We compared patients bridged with durable continuous-flow LVAD to those without LVAD support. Primary outcomes were ARF requiring HD before discharge following HT and CKD (defined as creatinine >2.5 mg/dl, permanent dialysis, or renal transplant) within 3 years. There were 18,738 patients, with 4,535 (24%) bridged with LVAD support. Left ventricular assist device patients had higher incidence of ARF requiring HD and CKD at 1 year, but no significant difference in CKD at 3 years compared to non-LVAD patients. Among LVAD patients, body mass index (BMI) (odds ratio [OR] = 1.79, p < 0.001), baseline estimated glomerular filtration rate (eGFR) (OR = 0.43, p < 0.001), and ischemic time (OR = 1.28, p = 0.014) were significantly associated with ARF requiring HD. Similarly, BMI (hazard ratio [HR] = 1.49, p < 0.001), baseline eGFR (HR = 0.41, p < 0.001), pre-HT diabetes mellitus (DM) (HR = 1.37, p = 0.011), and post-HT dialysis before discharge (HR = 3.93, p < 0.001) were significantly associated with CKD. Left ventricular assist device patients have a higher incidence of ARF requiring HD and CKD at 1 year after HT compared with non-LVAD patients, but incidence of CKD is similar by 3 years. Baseline renal function, BMI, ischemic time, and DM can help identify LVAD patients at risk of ARF requiring HD or CKD following HT.
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Affiliation(s)
- Anjan Tibrewala
- Division of Cardiology, Department of Medicine, Northwestern University, Chicago, Illinois
| | - Kiran K Khush
- Division of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford, California
| | - Wida S Cherikh
- Research Department, United Network for Organ Sharing, Richmond, Virginia
| | - Julia Foutz
- Research Department, United Network for Organ Sharing, Richmond, Virginia
| | - Josef Stehlik
- Division of Cardiovascular Medicine, Department of Medicine, University of Utah, Salt Lake City, Utah
| | - Jonathan D Rich
- Division of Cardiology, Department of Medicine, Northwestern University, Chicago, Illinois
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30
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Li Z, Chen Y, Xiong J, Lyu Q, Jiang B. Renal Function Following Bariatric Surgery: a Literature Review of Potential Mechanisms. Obes Surg 2022; 32:1734-1740. [PMID: 35243602 DOI: 10.1007/s11695-022-05985-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2021] [Revised: 02/17/2022] [Accepted: 02/17/2022] [Indexed: 11/26/2022]
Abstract
Obesity is a major and independent risk factor for onset and progression of many renal diseases. Bariatric surgery (BS) improves renal function by improving obesity-related metabolic disorders. However, the procedure is also accompanied by renal risks, including acute kidney injury (AKI) and oxalate nephropathy. Here, we briefly review the history and principle of frequently applied technique for BS and summarize the comprehensive BS effect on kidney function. Importantly, we highlight the possible molecular mechanisms associated with the recovery of renal function to provide novel ideas for future studies and clinical applications.
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Affiliation(s)
- Zhixin Li
- Xiangya School of Medicine, Central South University, Changsha, China
| | - Yu Chen
- Xiangya School of Medicine, Central South University, Changsha, China
| | - Jinming Xiong
- Xiangya School of Medicine, Central South University, Changsha, China
| | - Qinglan Lyu
- Department of Pathophysiology, Sepsis Translational Medicine Key Laboratory of Hunan Province, Xiangya School of Medicine, Central South University, Changsha, 410013, China.
| | - Bimei Jiang
- Department of Pathophysiology, Sepsis Translational Medicine Key Laboratory of Hunan Province, Xiangya School of Medicine, Central South University, Changsha, 410013, China.
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31
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Balata MG, Helal AH, Mohamed AH, Habib AU, Awad M, Sherif M. Gouty arthritis and kidney function outcomes and serum uric acid level variations in obese patients following bariatric surgery. THE EGYPTIAN JOURNAL OF INTERNAL MEDICINE 2022. [DOI: 10.1186/s43162-021-00091-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Obesity is an independent risk factor for chronic kidney disease (CKD) and is the strongest known modifiable risk factor for hyperuricemia and gout. We aimed to discover the outcome of serum uric acid (SUA), gouty arthritis, and kidney function in obese patients after bariatric surgery and possible links with BMI variations.
Methods
Retrospective study has been performed in National Hospital in Riyadh, KSA, between Jan. 2018 to Jan. 2020. We studied only 98 patients who met our inclusion criteria. Patients followed-up at 1 month (for gouty attack only) postoperative, 3 months postoperative, and 6 months postoperative for body mass index (BMI), serum creatinine, dipstick urinalysis, SUA, and estimated glomerular filtration rate (eGFR). Radiological studies, medical history, follow up radiological studies, and clinical follow up were obtained from the hospital data system.
Results
A total of 98 patients with mean eGFR were 90.65 ± 29.34 ml/min/1.73 m2, mean SUA 5.56 ± 1.84 mg/dl, and mean BMI was 45.28 ± 7.25 kg/m2, at surgery. Mean BMI had decreased significantly to 38.52 ± 6.05 kg/m2 at 3 months and to 34.61 ± 5.35 kg/m2 at 6 months (P < 0.001). The mean GFR had improved significantly (99.14 ± 23.32 ml/min/1.73 m2) at 6 months (P < 0.001). Interestingly, proteinuria had resolved in 17 patients out of 23 patients at 6 months. Number of gouty attacks was decreased during the first month post-surgery (P < 0.001). SUA level was significantly decreased (4.32 ± 1.27 mg/dl) (P < 0.001). SUA showed significant negative correlations with eGFR at 3 months and positively significant correlations with BMI at 3 and 6 months. By multinomial logistic regression, BMI and initial eGFR were the independent predictive variables for the outcome of eGFR at 6 months, while male gender and initial SUA were the independent predictive variables on the outcome of SUA at 6 months. Postoperatively in gouty arthritis patients, the number of joints affected, patient global VAS assessment, and number of gouty attacks were significantly reduced (P < 0.001).
Conclusion
Bariatric surgery has been associated with reduction of BMI and subsequently reduction of SUA levels, gouty attacks, and improvement of eGFR.
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32
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Mackowiak-Lewandowicz K, Ostalska-Nowicka D, Zaorska K, Kaczmarek E, Zachwieja J, Witt M, Nowicki M. Chronic kidney disease predictors in obese adolescents. Pediatr Nephrol 2022; 37:2479-2488. [PMID: 35211791 PMCID: PMC8869344 DOI: 10.1007/s00467-021-05403-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Revised: 11/25/2021] [Accepted: 11/29/2021] [Indexed: 01/01/2023]
Abstract
BACKGROUND Glomerular hyperfiltration, initiating development of obesity-related glomerulopathy, results in an enlargement of the glomeruli and unsealing of the filtration barrier. It can be followed by adaptive focal segmental glomerulosclerosis and chronic kidney disease (CKD). The aim of the study was to determine the expression pattern of lipid metabolism and selected kidney damage markers in obese adolescents and to identify potential factors which can predict CKD. METHODS The study group consisted of 142 adolescents with a BMI z-score > 2. Sixty-two healthy and normal-weight individuals served as controls. The factors associated with the rate of glomerular filtration in obese adolescents were assessed by linear regression methods using univariate and multivariate analyses. The risk of developing CKD was estimated using the Fisher's exact test. RESULTS The study group was divided into "elevated," "normal," and "decreased" glomerular filtration rate (GFR) patients. Increased urine galectin-3 (Gal-3) concentration was diagnosed in all patients. "Decreased GFR" subjects expressed increased urine concentration of neutrophil gelatinase-associated lipocalin (NGAL) and daily megalin excretion. Thirty-nine study participants developed CKD. Increased uric acid (UA) concentration was associated with CKD development both in "normal" and "decreased GFR" patients. Additionally, in "normal" GFR patients, increased concentrations of cholesterol (Ch), triglycerides (TG), and NGAL were associated with CKD. CONCLUSIONS Increased serum concentrations of Ch, TG, and UA and increased urine concentration of NGAL might predict CKD development in obese adolescents with normal and decreased GFR. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Affiliation(s)
| | - Danuta Ostalska-Nowicka
- Department of Pediatric Nephrology and Hypertension, Poznan University of Medical Sciences, Poznan, Poland
| | - Katarzyna Zaorska
- Department of Histology and Embryology, Poznan University of Medical Sciences, Poznan, Poland
| | - Elzbieta Kaczmarek
- Department of Bioinformatics and Computational Biology, Poznan University of Medical Sciences, Poznan, Poland
| | - Jacek Zachwieja
- Department of Pediatric Nephrology and Hypertension, Poznan University of Medical Sciences, Poznan, Poland
| | - Martin Witt
- Department of Anatomy, Rostock Univ. Med. Ctr., Rostock, Germany
| | - Michal Nowicki
- Department of Histology and Embryology, Poznan University of Medical Sciences, Poznan, Poland.
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Kotsis V, Martinez F, Trakatelli C, Redon J. Impact of Obesity in Kidney Diseases. Nutrients 2021; 13:nu13124482. [PMID: 34960033 PMCID: PMC8703549 DOI: 10.3390/nu13124482] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Revised: 12/10/2021] [Accepted: 12/10/2021] [Indexed: 01/14/2023] Open
Abstract
The clinical consequences of obesity on the kidneys, with or without metabolic abnormalities, involve both renal function and structures. The mechanisms linking obesity and renal damage are well understood, including several effector mechanisms with interconnected pathways. Higher prevalence of urinary albumin excretion, sub-nephrotic syndrome, nephrolithiasis, increased risk of developing CKD, and progression to ESKD have been identified as being associated with obesity and having a relevant clinical impact. Moreover, renal replacement therapy and kidney transplantation are also influenced by obesity. Losing weight is key in limiting the impact that obesity produces on the kidneys by reducing albuminuria/proteinuria, declining rate of eGFR deterioration, delaying the development of CKD and ESKD, and improving the outcome of a renal transplant. Weight reduction may also contribute to appropriate control of cardiometabolic risk factors such as hypertension, metabolic syndrome, diabetes, and dyslipidemia which may be protective not only in renal damage but also cardiovascular disease. Lifestyle changes, some drugs, and bariatric surgery have demonstrated the benefits.
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Affiliation(s)
- Vasilios Kotsis
- 3rd Department of Internal Medicine, Hypertension-24h ABPM ESH Center of Excellence, Papageorgiou Hospital, Aristotle University of Thessaloniki, 564 29 Pavlos Melas, Greece; (V.K.); (C.T.)
| | - Fernando Martinez
- Internal Medicine Hospital Clínico de Valencia, 46010 Valencia, Spain;
| | - Christina Trakatelli
- 3rd Department of Internal Medicine, Hypertension-24h ABPM ESH Center of Excellence, Papageorgiou Hospital, Aristotle University of Thessaloniki, 564 29 Pavlos Melas, Greece; (V.K.); (C.T.)
| | - Josep Redon
- Internal Medicine Hospital Clínico de Valencia, 46010 Valencia, Spain;
- Cardiovascular and Renal Research Group, INCLIVA Research Institute, University of Valencia, 46010 Valencia, Spain
- CIBERObn Carlos III Institute, 28029 Madrid, Spain
- Correspondence:
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Abstract
The kidney is one of the target organs that may show health disorders as a result of obesity. Obesity-related glomerulopathy (ORG) is a kidney disease category based on a biopsy diagnosis that may occur secondary to obesity. Detailed clinicopathologic observations of ORG have provided significant knowledge regarding obesity-associated renal complications. Glomerulomegaly with focal segmental glomerulosclerosis of perihilar locations is a typical renal histopathologic finding in ORG, which has long been considered to represent a state of single-nephron glomerular hyperfiltration. This hypothesis was recently confirmed in ORG patients by estimating single-nephron glomerular filtration rate using a combined image analysis and biopsy-based stereology. Overshooting in glomerulotubular and tubuloglomerular interactions may lead to glomerular hyperfiltration/hypertension, podocyte failure, tubular protein-traffic overload, and tubulointerstitial scarring, constituting a vicious cycle of a common pathway to the further loss of functioning nephrons and the progression of kidney functional impairment.
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Affiliation(s)
- Nobuo Tsuboi
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
| | - Yusuke Okabayashi
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
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Li Cavoli G, Tortorici C, Bono L, Ferrantelli A, Azzolina V, Li Cavoli TV, Tralongo A. Comment on "Which Patients with Obesity Are at Risk for Renal Disease?". Nephron Clin Pract 2021; 145:732-733. [PMID: 34547754 DOI: 10.1159/000519048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2021] [Accepted: 08/08/2021] [Indexed: 11/19/2022] Open
Affiliation(s)
- Gioacchino Li Cavoli
- Nephrology Dialysis Renal Transplant Department, ARNAS Civico Di Cristina, Palermo, Italy
| | - Calogera Tortorici
- Nephrology Dialysis Renal Transplant Department, ARNAS Civico Di Cristina, Palermo, Italy
| | - Luisa Bono
- Nephrology Dialysis Renal Transplant Department, ARNAS Civico Di Cristina, Palermo, Italy
| | - Angelo Ferrantelli
- Nephrology Dialysis Renal Transplant Department, ARNAS Civico Di Cristina, Palermo, Italy
| | - Vitalba Azzolina
- Nephrology Dialysis Renal Transplant Department, ARNAS Civico Di Cristina, Palermo, Italy
| | | | - Angelo Tralongo
- Nephrology Dialysis Renal Transplant Department, ARNAS Civico Di Cristina, Palermo, Italy
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Choi WJ, Hong YA, Min JW, Koh ES, Kim HD, Ban TH, Kim YS, Kim YK, Shin SJ, Kim SY, Yang CW, Chang YK. Hypertriglyceridemia Is Associated with More Severe Histological Glomerulosclerosis in IgA Nephropathy. J Clin Med 2021; 10:jcm10184236. [PMID: 34575346 PMCID: PMC8493798 DOI: 10.3390/jcm10184236] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Revised: 08/29/2021] [Accepted: 09/14/2021] [Indexed: 11/16/2022] Open
Abstract
IgA nephropathy (IgAN) is a globally well-known primary glomerular nephropathy. Hypertriglyceridemia (HTG) is one factor contributing to atherosclerosis and is a common complication of renal failure. HTG is a significant risk factor for decreased renal function in patients with IgAN. We evaluated the association of HTG with the histopathological features of IgAN patients. A total of 480 patients diagnosed with IgAN via kidney biopsy from eight university hospitals affiliated with the College of Medicine of the Catholic University of Korea were included in the final cohort. Pathological features were evaluated by eight expert pathologists with hospital consensus. HTG was defined as a serum triglyceride (TG) level of ≥150 mg/dL. In the study population analysis, the HTG group was older, with more males; higher body mass index (BMI), low-density lipoprotein cholesterol (LDL-C) and spot urine protein ratio; and lower estimated glomerular filtration rate (eGFR). In the lipid profile analysis, eGFR was negatively correlated with TGs/ high-density lipoprotein cholesterol (HDL) and triglyceride-glucose index (TyG). Proteinuria positively correlated with TGs/HDL, non-HDL/HDL, LDL/HDL, TyG, TGs and LDL. The percentages of global sclerosis (GS), segmental sclerosis (SS) and capsular adhesion (CA), and the scores for mesangial matrix expansion (MME) and mesangial cell proliferation (MCP), were more elevated in the HTG group compared to the normal TG group. Multivariable linear regression analysis showed that the percentages of global sclerosis, segmental sclerosis and capsular adhesion, as well as the scores for mesangial matrix expansion and mesangial cell proliferation, were positively associated with TG level. In binary logistic regression, the HTG group showed a higher risk for global sclerosis and segmental sclerosis. In conclusion, HTG is a significant risk factor for glomerulosclerosis in IgAN.
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Affiliation(s)
- Won Jung Choi
- Department of Internal Medicine, Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Daejeon 34943, Korea; (W.J.C.); (Y.A.H.); (S.Y.K.)
| | - Yu Ah Hong
- Department of Internal Medicine, Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Daejeon 34943, Korea; (W.J.C.); (Y.A.H.); (S.Y.K.)
| | - Ji Won Min
- Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Bucheon 14647, Korea;
| | - Eun Sil Koh
- Department of Internal Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 07345, Korea;
| | - Hyung Duk Kim
- Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (H.D.K.); (C.W.Y.)
| | - Tae Hyun Ban
- Department of Internal Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 03476, Korea;
| | - Young Soo Kim
- Department of Internal Medicine, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu 11765, Korea;
| | - Yong Kyun Kim
- Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon 16247, Korea;
| | - Seok Joon Shin
- Department of Internal Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Incheon 22711, Korea;
| | - Seok Young Kim
- Department of Internal Medicine, Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Daejeon 34943, Korea; (W.J.C.); (Y.A.H.); (S.Y.K.)
| | - Chul Woo Yang
- Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (H.D.K.); (C.W.Y.)
| | - Yoon-Kyung Chang
- Department of Internal Medicine, Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Daejeon 34943, Korea; (W.J.C.); (Y.A.H.); (S.Y.K.)
- Correspondence:
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Aiumtrakul N, Kittithaworn A, Supasyndh O, Krittayaphong R, Phrommintikul A, Satirapoj B. Association of body mass index with kidney function and mortality in high cardiovascular risk population: A nationwide prospective cohort study. Nephrology (Carlton) 2021; 27:25-34. [PMID: 34463405 DOI: 10.1111/nep.13970] [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: 08/01/2021] [Revised: 08/25/2021] [Accepted: 08/29/2021] [Indexed: 11/28/2022]
Abstract
BACKGROUND There is increasing awareness of the impact of obesity and underweight on cardiovascular (CV) disease, chronic kidney disease (CKD) and mortality. Abnormal body mass index (BMI) might be associated with worse clinical outcomes, including CKD progression, but limited evidence exists among Asian patients with high CV risk. OBJECTIVE To investigate the association of BMI with progressive loss of kidney function and all-cause mortality in Thai patients with high CV risk. METHODS In a national cohort of 5887 high CV risk subjects, we assessed the association of high BMI with the composite renal outcome (estimated glomerular filtration rate [eGFR] decline over 40%, eGFR less than 15 mL/min/1.73 m2 , doubling of serum creatinine, initiation of dialysis and death related to renal causes) and with all-cause mortality in Cox proportional hazards models. RESULTS A total of 5887 participants (3217 male and 2670 female) with high CV risk were enrolled. Participants were classified into five groups by their baseline BMI; <20 kg/m2 (n = 482), 20-24.9 kg/m2 (n = 2437), 25-29.9 kg/m2 (n = 2140), 30-34.9 kg/m2 (n = 665) and 35 kg/m2 (n = 163), respectively. On multivariate analysis of Cox proportional hazards models, adjusted for other covariates, baseline BMI ≥35 kg/m2 was an independent predictor of loss of kidney function (HR 1.60, 95% CI 1.04-2.40) and all-cause mortality (HR 2.68, 95% CI 1.50-4.80). Baseline BMI <20 kg/m2 was an independent predictor of all-cause mortality as well (adjusted HR 2.26, 95% CI 1.50-3.42). CONCLUSION In the high CV risk Thai population, a BMI of 35 kg/m2 or more is associated with loss of kidney function and mortality. On the other hand, a BMI less than 20 kg/m2 is also associated with all-cause mortality.
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Affiliation(s)
- Noppawit Aiumtrakul
- Division of Nephrology, Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand
| | - Annop Kittithaworn
- Division of Nephrology, Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand
| | - Ouppatham Supasyndh
- Division of Nephrology, Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand
| | - Rungroj Krittayaphong
- Division of Cardiology, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Arintaya Phrommintikul
- Division of Cardiology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Bancha Satirapoj
- Division of Nephrology, Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand
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Differences between Obese and Non-Obese Children and Adolescents Regarding Their Oral Status and Blood Markers of Kidney Diseases. J Clin Med 2021; 10:jcm10163723. [PMID: 34442019 PMCID: PMC8397190 DOI: 10.3390/jcm10163723] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Revised: 08/11/2021] [Accepted: 08/17/2021] [Indexed: 01/05/2023] Open
Abstract
(1) Background: A rarely discussed effect of obesity-related glomerulopathy (ORG) may slowly lead to irreversible glomerular damage and the development of chronic kidney disease. These patients need to undertake medical care, but whether they should be included in intensive oral care is still not mandatory. The study aimed to assess a relationship between renal, metabolic, and oral health indicators among pediatric patients affected by simple obesity. (2) Methods: 45 children and adolescents with simple obesity hospitalized (BMI 34.1 ± 4.8 kg/m2, age 15.4 ± 2.3) and compared with 41 aged-matched healthy controls (BMI 16.4 ± 2.4 kg/m2, age 15.4 ± 2.7). Echocardiography, 24-h ambulatory blood pressure monitoring, ultrasound exam with Doppler, and laboratory tests including kidney and metabolic markers were performed. Oral status was examined regarding the occurrence of carious lesions using decay missing filling teeth (DMFT), gingivitis as bleeding on probing (BOP), and bacterial colonization as plaque control record (PCR). (3) Results: The strongest correlation was revealed between BMI and concentration of uric acid, cystatin C, GFR estimated by the Filler formula (r = 0.74; r = 0.48; r = -0.52), and between oral variables such as PCR and BOP (r = 0.54; r = 0.58). Children and adolescents with obesity demonstrated untreated dental caries, less efficient in plaque control and gingivitis. (4) Conclusions: No specific relation to markers of kidney disease were found; however, more frequent gingivitis/bacterial colonization and significant differences in oral status between obese and non-obese patients were revealed. Susceptibility to inflammation may be conducive to developing metabolic syndrome and kidney damage in the form of obesity-related glomerulopathy and contribute to future dental caries. Uric acid seems to indicate metabolic syndrome and cardiovascular complications (LVMI > 95 percentiles). Cystatin C and uric acid might aspire to be early markers of kidney damage leading to obesity-related glomerulopathy.
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Sangartit W, Ha KB, Lee ES, Kim HM, Kukongviriyapan U, Lee EY, Chung CH. Tetrahydrocurcumin Ameliorates Kidney Injury and High Systolic Blood Pressure in High-Fat Diet-Induced Type 2 Diabetic Mice. Endocrinol Metab (Seoul) 2021; 36:810-822. [PMID: 34474516 PMCID: PMC8419617 DOI: 10.3803/enm.2021.988] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Accepted: 05/25/2021] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Activation of the intrarenal renin-angiotensin system (RAS) is implicated in the pathogenesis of kidney injury and hypertension. We aimed to investigate the protective effect of tetrahydrocurcumin (THU) on intrarenal RAS expression, kidney injury, and systolic blood pressure (SBP) in high-fat diet (HFD)-induced type 2 diabetic mice. METHODS Eight-week-old male mice were fed a regular diet (RD) or HFD for 12 weeks, and THU (50 or 100 mg/kg/day) was intragastrically administered with HFD. Physiological and metabolic changes were monitored and the expression of RAS components and markers of kidney injury were assessed. RESULTS HFD-fed mice exhibited hyperglycemia, insulin resistance, and dyslipidemia compared to those in the RD group (P<0.05). Kidney injury in these mice was indicated by an increase in the ratio of albumin to creatinine, glomerular hypertrophy, and the effacement of podocyte foot processes. Expression of intrarenal angiotensin-converting enzyme, angiotensin II type I receptor, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-4, and monocyte chemoattractant protein-1 was also markedly increased in HFD-fed mice. HFD-fed mice exhibited elevated SBP that was accompanied by an increase in the wall thickness and vascular cross-sectional area (P<0.05), 12 weeks post-HFD consumption. Treatment with THU (100 mg/kg/day) suppressed intrarenal RAS activation, improved insulin sensitivity, and reduced SBP, thus, attenuating kidney injury in these mice. CONCLUSION THU alleviated kidney injury in mice with HFD-induced type 2 diabetes, possibly by blunting the activation of the intrarenal RAS/nicotinamide adenine dinucleotide phosphate oxidase IV (NOX4)/monocyte chemoattractant protein 1 (MCP-1) axis and by lowering the high SBP.
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Affiliation(s)
- Weerapon Sangartit
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju,
Korea
- Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen,
Thailand
- Cardiovascular Research Group, Khon Kaen University, Khon Kaen,
Thailand
| | - Kyung Bong Ha
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju,
Korea
| | - Eun Soo Lee
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju,
Korea
- Institution of Genetic Cohort, Yonsei University Wonju College of Medicine, Wonju,
Korea
| | | | - Upa Kukongviriyapan
- Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen,
Thailand
- Cardiovascular Research Group, Khon Kaen University, Khon Kaen,
Thailand
| | - Eun Young Lee
- Department of Internal Medicine and Institute of Tissue Regeneration, BK21 FOUR Project, Soonchunhyang University College of Medicine, Cheonan,
Korea
| | - Choon Hee Chung
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju,
Korea
- Institution of Genetic Cohort, Yonsei University Wonju College of Medicine, Wonju,
Korea
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Wu J, Lai G, Chen F, Zhang B, Zhao Y. Renal NKCC2 Is Dual Regulated by the Synergy of 20-HETE and High-Fat Diet in CYP4F2 Transgenic Mice. Kidney Blood Press Res 2021; 46:601-612. [PMID: 34320496 DOI: 10.1159/000517382] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Accepted: 04/22/2021] [Indexed: 11/19/2022] Open
Abstract
INTRODUCTION 20-Hydroxyeicosatetraenoic acid (20-HETE) is the metabolite of cytochrome P450, which modulates blood pressure by inhibiting renal sodium transport. However, the molecular mechanisms underlying the role of 20-HETE in the development of obesity-related hypertension remain unclear, necessitating this study. METHODS Cytochrome P450 4F2 (CYP4F2) transgenic mice fed high-fat diet (HFD) were used as research animal models. The expression of renal ion transport molecules targeted by 20-HETE was evaluated by real-time PCR and Western blot (WB). The regulatory effect of 20-HETE and HFD on renal Na+-K+-2Cl- cotransporter, isoform 2 (NKCC2) was explored by immunoprecipitation, WB, and luciferase assay. RESULTS A 2-week HFD feeding dramatically decreased protein abundance but increased renal NKCC2 mRNA expression in CYP4F2 transgenic mice. The decrease in NKCC2 protein was demonstrated to be due to ubiquitination induced by the synergy between 20-HETE and HFD. The increased PPAR-γ protein in CYP4F2 transgenic mice fed HFD and the activation of rosiglitazone on the luciferase reporter construct of the NKCC2 promoter demonstrated that the increase in NKCC2 mRNA in CYP4F2 transgenic mice fed HFD was a consequence of elevated PPAR-γ protein induced by the synergy between 20-HETE and HFD. CONCLUSIONS Our data demonstrated that the synergy between 20-HETE and HFD could decrease NKCC2 protein via posttranslational ubiquitination, which was thought to be the main mechanism underlying the short-term effect in response to HFD and might be responsible for the adaptive modulation of renal NKCC2 to resist sodium retention. Moreover, the increased NKCC2 mRNA expression via PPAR-γ-induced transcriptional regulation was thought to be the main mechanism underlying the long-term effect in response to HFD and plays a pivotal role in the development of obesity-related hypertension.
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Affiliation(s)
- Jingjing Wu
- Department of Medical Genetics, School of Life Sciences, China Medical University, Shenyang, China,
| | - Guangrui Lai
- Department of Clinical Genetics, Shengjing Hospital of China Medical University, Shenyang, China
| | - Fangjie Chen
- Department of Medical Genetics, School of Life Sciences, China Medical University, Shenyang, China
| | - Bijun Zhang
- Department of Clinical Genetics, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yanyan Zhao
- Department of Medical Genetics, School of Life Sciences, China Medical University, Shenyang, China
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Yamasaki N, Sakurai M, Kobayashi J, Morikawa Y, Kido T, Naruse Y, Nogawa K, Suwazono Y, Ishizaki M, Nakagawa H. The Association between Anthropometric Indices of Obesity and Chronic Kidney Disease in Middle-aged Japanese Men and Women: A Cohort Study. Intern Med 2021; 60:2007-2015. [PMID: 33551403 PMCID: PMC8313930 DOI: 10.2169/internalmedicine.6235-20] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
Objective This study investigated associations between three indices of obesity-the body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR)-and the incidence of chronic kidney disease (CKD). Methods The employees of a company in Japan (1,725 men, 1,186 women; aged 35-55 years) had BMI, WC, and WHtR measured in health examinations. The incidence of CKD was determined at annual medical examinations over a six-year period. The hazard ratios for CKD were calculated using proportional hazard models, and the χ2 statistic was used to compare the strengths of the associations. Results The mean BMI (kg/m2), WC (cm), and WHtR were 23.6, 84.3, and 0.49 for men and 22.3, 79.7, and 0.50 for women, respectively. The incidence of CKD (/1,000 person-years) was 18.1 for men and 8.4 for women. In men, positive linear associations were observed between the BMI, WC, and WHtR and the risk of CKD, even after adjusting for the presence of metabolic abnormalities (p for trend <0.001, 0.012, and 0.023, respectively). In women, a linear association was observed only between the WHtR and CKD, not the BMI or WC (p for trend =0.042, 0.057, and 0.186). The χ2 statistics were the highest for the BMI in both men and women. Conclusion The BMI, WC, and WHtR were linearly associated with the risk of CKD independently of metabolic abnormalities in men, while the associations were weaker or not significant in women. The BMI was the most strongly associated with the incidence of CKD in both men and women.
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Affiliation(s)
- Naruhiro Yamasaki
- Department of General Internal Medicine, Kanazawa Medical University, Japan
| | - Masaru Sakurai
- Department of Social and Environmental Medicine, Kanazawa Medical University, Japan
- Health Evaluation Center, Kanazawa Medical University, Japan
| | - Junji Kobayashi
- Department of Endocrinology, Hematology and Gerontology, Graduate School of Medicine, Chiba University, Japan
| | - Yuko Morikawa
- School of Nursing, Kanazawa Medical University, Japan
| | - Teruhiko Kido
- School of Health Sciences, College of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Japan
| | | | - Kazuhiro Nogawa
- Department of Occupation and Environmental Medicine, Graduate School of Medicine, Chiba University, Japan
| | - Yasushi Suwazono
- Department of Occupation and Environmental Medicine, Graduate School of Medicine, Chiba University, Japan
| | - Masao Ishizaki
- Department of Social and Environmental Medicine, Kanazawa Medical University, Japan
- Health Evaluation Center, Kanazawa Medical University, Japan
| | - Hideaki Nakagawa
- Department of Social and Environmental Medicine, Kanazawa Medical University, Japan
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Zhang T, Wang Y, Zhang X, Wang W, Zhao G. The Impact of Bariatric Surgery on Renal Function: a Retrospective Analysis of Short-Term Outcomes. Obes Surg 2021; 31:3476-3482. [PMID: 34061302 DOI: 10.1007/s11695-021-05366-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Revised: 03/16/2021] [Accepted: 03/19/2021] [Indexed: 12/13/2022]
Abstract
PURPOSE Obesity and diabetes mellitus are now leading causes of chronic kidney disease. Our study investigated the effects of bariatric surgery on estimated glomerular filtration (eGFR) and urinary microalbumin/creatinine ratio (ACR) in morbidly obese patients. MATERIALS AND METHODS The clinical materials for patients who underwent bariatric surgery were retrospectively analyzed with a 6-month follow-up period between January 1, 2018, and June 1, 2020. The eGFR (ml/min) was calculated using the Cockcroft-Gault formula equation. The urinary ACR was measured during the follow-up. Body mass index (BMI, kg/m2), percent weight loss (%WL), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were recorded during the follow-up. RESULTS Sixty-one patients who underwent bariatric surgery-laparoscopic Roux-en-Y gastric bypass (LRYGB; n = 22) and laparoscopic sleeve gastrectomy (LSG; n = 39)-were included in this study. The eGFR of both groups decreased at the follow-up outpatient visits (p < 0.001), although eGFR did not differ between the two groups. Unexpectedly, the ACR increased in the first month after LSG (p < 0.01) but decreased with a descending trend with no significant difference (p > 0.05) throughout the remaining follow-up period. Interestingly, ACR showed a descending trend with no significant difference during the follow-up in the LRYGB group (p > 0.05). The SBP and DBP decreased after bariatric surgery, with no significant difference between the two groups (p > 0.05). CONCLUSION Bariatric surgery is associated with improvements in postoperative renal function 6 months following surgery. The different alterations in ACR following LSG and LRYGB procedures demonstrate the underlying mechanism.
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Affiliation(s)
- Taotao Zhang
- Department of General Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang City, 110032, Liaoning Province, China.,The Second Gastric & Intestinal Department, Dalian Municipal Central Hospital Affiliated of Dalian Medical University, Dalian City, 116033, Liaoning Province, China
| | - Yong Wang
- Department of General Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang City, 110032, Liaoning Province, China.
| | - Xiangwen Zhang
- The Second Gastric & Intestinal Department, Dalian Municipal Central Hospital Affiliated of Dalian Medical University, Dalian City, 116033, Liaoning Province, China
| | - Wendi Wang
- The Fourth Obstetrics Ward, Dalian Maternal and Childcare Health Hospital Affiliated of Dalian Medical University, Dalian City, 116033, Liaoning Province, China
| | - Guohua Zhao
- The Second Gastric & Intestinal Department, Dalian Municipal Central Hospital Affiliated of Dalian Medical University, Dalian City, 116033, Liaoning Province, China
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Effects of Virgin Olive Oil on Blood Pressure and Renal Aminopeptidase Activities in Male Wistar Rats. Int J Mol Sci 2021; 22:ijms22105388. [PMID: 34065436 PMCID: PMC8161085 DOI: 10.3390/ijms22105388] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2021] [Revised: 05/16/2021] [Accepted: 05/18/2021] [Indexed: 12/15/2022] Open
Abstract
High saturated fat diets have been associated with the development of obesity and hypertension, along with other pathologies related to the metabolic syndrome. In contrast, the Mediterranean diet, characterized by its high content of monounsaturated fatty acids, has been proposed as a dietary factor capable of positively regulating cardiovascular function. These effects have been linked to changes in the local renal renin angiotensin system (RAS) and the activity of the sympathetic nervous system. The main goal of this study was to analyze the role of two dietary fat sources on aminopeptidases activities involved in local kidney RAS. Male Wistar rats (six months old) were fed during 24 weeks with three different diets: the standard diet (S), the standard diet supplemented with virgin olive oil (20%) (VOO), or the standard diet enriched with butter (20%) plus cholesterol (0.1%) (Bch). Kidney samples were separated in medulla and cortex for aminopeptidase activities (AP) assay. Urine samples were collected for routine analysis by chemical tests. Aminopeptidase activities were determined by fluorometric methods in soluble (sol) and membrane-bound (mb) fractions of renal tissue, using arylamide derivatives as substrates. After the experimental period, the systolic blood pressure (SBP) values were similar in standard and VOO animals, and significantly lower than in the Bch group. At the same time, a significant increase in GluAP and IRAP activities were found in renal medulla of Bch animals. However, in VOO group the increase of GluAP activity in renal medulla was lower, while AspAP activity decreased in the renal cortex. Furthermore, the VOO diet also affected other aminopeptidase activities, such as TyrAP and pGluAP, related to the regulation of the sympathetic nervous system and the metabolic rate. These results support the beneficial effect of VOO in the regulation of SBP through changes in local AP activities of the kidney.
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Torguet Escuder P. [Obesity, chronic kidney disease and cardiovascular risk]. HIPERTENSION Y RIESGO VASCULAR 2021; 38:53-55. [PMID: 33752844 DOI: 10.1016/j.hipert.2021.03.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 03/09/2021] [Accepted: 03/09/2021] [Indexed: 11/25/2022]
Affiliation(s)
- P Torguet Escuder
- Servicio de Nefrologia, Hospital Universitario Dr J. Trueta, Girona, España.
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Shah PP, Brady TM, Meyers KEC, O'Shaughnessy MM, Gibson KL, Srivastava T, Zee J, Cattran D, Tuttle KR, Gadegbeku C, Glenn D, Derebail V, Smith A, Wang CS, Gillespie BW, Bitzer M, Sethna CB. Association of Obesity with Cardiovascular Risk Factors and Kidney Disease Outcomes in Primary Proteinuric Glomerulopathies. Nephron Clin Pract 2021; 145:245-255. [PMID: 33677435 DOI: 10.1159/000513869] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Accepted: 12/16/2020] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND/AIMS Obesity is a known risk factor for cardiovascular disease and contributes to the development and progression of kidney disease. However, the specific influence of obesity on outcomes in primary glomerular disease has not been well characterized. METHODS In this prospective cohort study, data were from 541 participants enrolled in the Nephrotic Syndrome Study Network (NEPTUNE), between 2010 and 2019, at 23 sites across North America. Blood pressure, lipids, and kidney disease outcomes including complete proteinuria remission, kidney failure, and chronic kidney disease progression were evaluated. Data were analyzed using linear and logistic regression with generalized estimating equations and time-varying Cox regression with Kaplan-Meier plots. RESULTS The prevalence of obesity at baseline was 43.3% (N = 156) in adults and 37.6% (N = 68) in children. In adults, obesity was longitudinally associated with higher systolic BP (β = 6.49, 95% CI: 2.41, 10.56, p = 0.002), dyslipidemia (OR = 1.74, 95% CI: 1.30, 2.32, p < 0.001), triglycerides (β = 41.92, 95% CI: 17.12, 66.71, p = 0.001), and lower HDL (β = -6.92, 95% CI: -9.32, -4.51, p < 0.001). In children, obesity over time was associated with higher systolic BP index (β = 0.04, 95% CI: 0.02, 0.06, p < 0.001) and hypertension (OR = 1.43, 95% CI: 1.04, 1.98, p = 0.03). In both adults and children, obesity was associated with a significantly lower hazard of achieving complete remission of proteinuria (adult HR = 0.80, 95% CI: 0.69, 0.88, p < 0.001; pediatric HR = 0.72, 95% CI: 0.61, 0.84, p < 0.001). CONCLUSION Obesity was associated with higher cardiovascular risk and less proteinuria remission from nephrotic syndrome in adults and children with proteinuric glomerulopathies. Weight-loss strategies may forestall cardiovascular disease and progressive kidney function decline in this high-risk patient group.
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Affiliation(s)
- Paras P Shah
- Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, USA
| | - Tammy M Brady
- Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Kevin E C Meyers
- The Children Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania, USA.,Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | | | - Keisha L Gibson
- UNC Kidney Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
| | | | - Jarcy Zee
- Arbor Research Collaborative for Health, Ann Arbor, Michigan, USA
| | - Daniel Cattran
- Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada
| | - Katherine R Tuttle
- Providence Health Care, University of Washington, Spokane, Washington, USA
| | - Crystal Gadegbeku
- Temple University School of Medicine, Philadelphia, Pennsylvania, USA
| | - Dorey Glenn
- UNC Kidney Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
| | - Vimal Derebail
- UNC Kidney Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
| | - Abigail Smith
- Arbor Research Collaborative for Health, Ann Arbor, Michigan, USA
| | - Chia-Shi Wang
- Emory University School of Medicine, Atlanta, Georgia, USA
| | - Brenda W Gillespie
- Consulting for Statistics, Computing and Analytics Research and School of Public Health, University of Michigan, Ann Arbor, Michigan, USA
| | - Markus Bitzer
- Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Christine B Sethna
- Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, USA, .,Cohen Children's Medical Center of NY, New Hyde Park, New York, USA,
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Sucedaram Y, Johns EJ, Husain R, Abdul Sattar M, H Abdulla M, Nelli G, Rahim NS, Khalilpourfarshbafi M, Abdullah NA. Exposure to High-Fat Style Diet Induced Renal and Liver Structural Changes, Lipid Accumulation and Inflammation in Intact and Ovariectomized Female Rats. J Inflamm Res 2021; 14:689-710. [PMID: 33716510 PMCID: PMC7944944 DOI: 10.2147/jir.s299083] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2020] [Accepted: 02/18/2021] [Indexed: 12/17/2022] Open
Abstract
Purpose We hypothesized that low estrogen levels aggravate obesity-related complications. Diet-induced obesity can cause distinct pathologies, including impaired glucose tolerance, inflammation, and organ injury that leads to fatty liver and chronic kidney diseases. To test this hypothesis, ovariectomized (OVX) rats were fed a high-fat style diet (HFSD), and we examined structural changes and inflammatory response in the kidney and liver. Methods Sprague-Dawley female rats were ovariectomized or sham-operated and divided into four groups: sham-operated rats fed a normal diet (ND); ovariectomized rats fed a normal diet (OVX-ND); sham-operated rats fed a HFSD; ovariectomized rats fed a high-fat style diet (OVX-HFSD). Mean blood pressure and fasting blood glucose were measured on weeks 0 and 10. The rats were sacrificed 10 weeks after initiation of ND or HFSD, the kidney and liver were harvested for histological, immunohistochemical and immunofluorescence studies. Results HFSD-fed rats presented a significantly greater adiposity index compared to their ND counterparts. Liver index, fasting blood glucose and mean blood pressure was increased in OVX-HFSD rats compared to HFSD rats at study terminal. Histological and morphometric studies showed focal interstitial mononuclear cell infiltration in the kidney of HFSD rats with mesangial expansion being greater in the OVX-HFSD rats. Both HFSD fed groups showed increased expressions of renal inflammatory markers, namely TNF-alpha, IL-6 and MCP-1, and infiltrating M1 macrophages with some influence of ovarian hormonal status. HFSD-feeding also caused hepatocellular steatosis which was aggravated in ovariectomized rats fed the same diet. Furthermore, hepatocellular ballooning was observed only in the OVX-HFSD rats. Similarly, HFSD-fed rats showed increased expressions of the inflammatory markers and M1 macrophage infiltration in the liver; however, only IL-6 expression was magnified in the OVX-HFSD. Conclusion Our data suggest that some of the structural changes and inflammatory response in the kidney and liver of rats fed a HFSD are exacerbated by ovariectomy.
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Affiliation(s)
- Yamuna Sucedaram
- Department of Pharmacology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, 50603, Malaysia
| | - Edward James Johns
- Department of Physiology, University College Cork, Cork, T12 K8AF, Ireland
| | - Ruby Husain
- Department of Physiology, Universiti Malaya, Kuala Lumpur, 50603, Malaysia
| | - Munavvar Abdul Sattar
- School of Pharmaceutical Sciences, Universiti Sains Malaysia, Gelugor, 11800, Pulau Pinang, Malaysia
| | - Mohammed H Abdulla
- Department of Physiology, University College Cork, Cork, T12 K8AF, Ireland
| | - Giribabu Nelli
- Department of Physiology, Universiti Malaya, Kuala Lumpur, 50603, Malaysia
| | - Nur Syahrina Rahim
- Faculty of Medicine & Health Science, Universiti Sains Islam Malaysia, Nilai, 71800, Malaysia
| | | | - Nor Azizan Abdullah
- Department of Pharmacology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, 50603, Malaysia
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Remission and progression of pre-existing micro- and macroalbuminuria over 15 years after bariatric surgery in Swedish Obese Subjects study. Int J Obes (Lond) 2020; 45:535-546. [PMID: 33159178 PMCID: PMC7914157 DOI: 10.1038/s41366-020-00707-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Revised: 09/24/2020] [Accepted: 10/23/2020] [Indexed: 01/22/2023]
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Liang R, Wang M, Fu C, Liang H, Deng H, Tan Y, Xu F, Cai M. Liraglutide protects against high-fat diet-induced kidney injury by ameliorating apoptosis. Endocr Connect 2020; 9:946-954. [PMID: 33027757 PMCID: PMC7583131 DOI: 10.1530/ec-20-0294] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Accepted: 09/03/2020] [Indexed: 12/16/2022]
Abstract
BACKGROUND Obesity is associated with the development and progression of chronic kidney disease. Emerging evidence suggests that glucagon-like peptide-1 receptor agonist could reduce renal damage and albuminuria. Sirtuin 1 (SIRT1) was considered as a crucial regulator in metabolism-related kidney disease. Herein, the role of SIRT1 in liraglutide-ameliorated high-fat diet (HFD)-induced kidney injury was illustrated. METHODS Male C57BL/6 mice were fed HFD for 20 weeks to induce kidney injury that was then treated with liraglutide for 8 weeks to estimate its protective effect on the kidney. Also, the mechanism of the drug in SV40 MES 13 (SV40) mouse mesangial cells was elucidated. RESULTS Liraglutide treatment ameliorated HFD-induced metabolic disorders, including hyperglycemia, increasing body weight, and insulin resistance. In addition, kidney weight, urine albumin-to-creatinine, and kidney morphological changes such as vacuolated tubules, glomerulomegaly, thickened glomerular basement membrane, and tubulointerstitial fibrosis were also significantly ameliorated. Furthermore, apoptotic cells and apoptosis markers were downregulated in the kidney of liraglutide-treated mice. In addition, the expression of SIRT1 protein was upregulated, whereas thioredoxin-interacting protein (TXNIP), which serves as a mediator of oxidative stress and apoptosis in metabolism disease, was downregulated by liraglutide. In SV40 cells, the effect of liraglutide on reversing the upregulation of cleaved caspase-3 induced by high glucose (30 mM) was hampered when SIRT1 was knocked down; also, the downregulation of TXNIP by liraglutide was blocked. CONCLUSIONS Liraglutide might have a beneficial effect on metabolism-related kidney damage by inhibiting apoptosis via activation of SIRT1 and suppression of TXNIP pathway.
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Affiliation(s)
- Riying Liang
- Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, China
- Department of Ultrasound, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Meijun Wang
- Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, China
| | - Chang Fu
- Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, China
| | - Hua Liang
- Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, China
| | - Hongrong Deng
- Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, China
| | - Ying Tan
- Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, China
| | - Fen Xu
- Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, China
| | - Mengyin Cai
- Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, China
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Hong YA, Min JW, Ha MA, Koh ES, Kim HD, Ban TH, Kim YS, Kim YK, Kim D, Shin SJ, Choi WJ, Chang YK, Kim SY, Park CW, Kim YO, Yang CW, Yoon HE. The Impact of Obesity on the Severity of Clinicopathologic Parameters in Patients with IgA Nephropathy. J Clin Med 2020; 9:jcm9092824. [PMID: 32878271 PMCID: PMC7564413 DOI: 10.3390/jcm9092824] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Accepted: 08/15/2020] [Indexed: 01/22/2023] Open
Abstract
Several studies reported the effect of obesity on the progression of IgA nephropathy (IgAN). However, the impact of obesity on the clinicopathologic presentation of IgAN remains uncertain. This is a retrospective cross-sectional study from eight university hospitals in South Korea. Patients were categorized into three groups using the Asia-Pacific obesity classification based on body mass index (BMI). Clinical and histopathologic data at the time of renal biopsy were analyzed. Among 537 patients with IgAN, the obese group was more hypertensive and had lower estimated glomerular filtration rate and more proteinuria than other groups. The histologic scores for mesangial matrix expansion (MME), interstitial fibrosis, tubular atrophy, and mesangial C3 deposition differed significantly between the three groups. Among these histopathologic parameters, BMI was independently positively associated with MME score on multivariable linear regression analysis (p = 0.028). Using multivariable logistic regression analysis, the obese group was independently associated with higher MME scores compared to the normal weight/overweight group (p = 0.020). However, BMI was not independently associated with estimated glomerular filtration rate or proteinuria on multivariable analysis. Obesity was independently associated with severe MME in patients with IgAN. Obesity may play an important pathogenetic role in mesangial lesions seen in IgAN.
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Affiliation(s)
- Yu Ah Hong
- Department of Internal Medicine, Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Daejeon 34943, Korea; (Y.A.H.); (W.J.C.); (Y.K.C.); (S.Y.K.)
| | - Ji Won Min
- Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Bucheon 14647, Korea; (J.W.M.); (M.A.H.)
| | - Myung Ah Ha
- Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Bucheon 14647, Korea; (J.W.M.); (M.A.H.)
| | - Eun Sil Koh
- Department of Internal Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 07345, Korea;
| | - Hyung Duk Kim
- Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (H.D.K.); (C.W.P.); (C.W.Y.)
| | - Tae Hyun Ban
- Department of Internal Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 03476, Korea;
| | - Young Soo Kim
- Department of Internal Medicine, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu 11765, Korea; (Y.S.K.); (Y.O.K.)
| | - Yong Kyun Kim
- Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon 16247, Korea;
| | - Dongryul Kim
- Department of Internal Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Incheon 22711, Korea; (D.K.); (S.J.S.)
| | - Seok Joon Shin
- Department of Internal Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Incheon 22711, Korea; (D.K.); (S.J.S.)
| | - Won Jung Choi
- Department of Internal Medicine, Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Daejeon 34943, Korea; (Y.A.H.); (W.J.C.); (Y.K.C.); (S.Y.K.)
| | - Yoon Kyung Chang
- Department of Internal Medicine, Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Daejeon 34943, Korea; (Y.A.H.); (W.J.C.); (Y.K.C.); (S.Y.K.)
| | - Suk Young Kim
- Department of Internal Medicine, Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Daejeon 34943, Korea; (Y.A.H.); (W.J.C.); (Y.K.C.); (S.Y.K.)
| | - Cheol Whee Park
- Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (H.D.K.); (C.W.P.); (C.W.Y.)
| | - Young Ok Kim
- Department of Internal Medicine, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu 11765, Korea; (Y.S.K.); (Y.O.K.)
| | - Chul Woo Yang
- Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (H.D.K.); (C.W.P.); (C.W.Y.)
| | - Hye Eun Yoon
- Department of Internal Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Incheon 22711, Korea; (D.K.); (S.J.S.)
- Correspondence: ; Tel.: +82-32-280-5886
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Albuminuria in Patients with Morbid Obesity and the Effect of Weight Loss Following Bariatric Surgery. Obes Surg 2020; 29:3581-3588. [PMID: 31240536 DOI: 10.1007/s11695-019-04036-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND AND OBJECTIVES Patients with morbid obesity are at an increased risk for cardiovascular and renal complications, which are not only linked to traditional cardiovascular risk factors. Thus, we evaluated (a) the prevalence of albuminuria in non-diabetic and diabetic morbidly obese patients and (b) the effect of weight loss following bariatric surgery. MATERIAL AND METHODS We included 1307 patients (77% women, mean age 40 ± 12 years, BMI 45.6 ± 6.6 kg/m2) in a cross-sectional study. A subgroup (n = 318) was followed up for 2 years after bariatric surgery. Weight, cardiovascular risk markers and a 75-g glucose tolerance test were determined. Albuminuria was assessed by collecting 24-h urine on three consecutive days. RESULTS In the cross-sectional study, the prevalence of microalbuminuria was 16.0% (n = 209), of macroalbuminuria 3.1% (n = 41). The chi-square for the association of albuminuria and diabetes was 31.937 (p < 0.001). Of all patients with albuminuria, 42.0% exhibited normal glucose tolerance. In a multivariate regression analysis, systolic blood pressure (beta = 0.236; p < 0.001), log fasting insulin (beta = 0.309; p < 0.001) and log 2-h postprandial insulin (beta = - 0.173; p = 0.033) were predictive risk factors for albuminuria. Longitudinally, albumin excretion decreased significantly from 11.1 (6.4, 18.4 mg/24 h) to 7.8 mg/24 h (4.9, 13.0 mg/24 h; p < 0.001). In the group with albuminuria preoperatively, albumin excretion decreased from 65.7 (38.2, 147.1 mg/24 h) to 13.5 mg/24 h (8.4, 36.8 mg/24 h; p < 0.001). After adjusting for age, sex and baseline albuminuria, patients with lower creatinine clearance showed a smaller decrease of albuminuria (beta = 0.117; p = 0.021). CONCLUSION A substantial portion of patients with morbid obesity exhibits microalbuminuria, nearly half of those present with normal glucose tolerance. After weight loss, we found a significant decrease of albuminuria, potentially indicating or even contributing to the known reduction of cardiovascular mortality after bariatric surgery.
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