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1
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Petrie JR. Metformin beyond type 2 diabetes: Emerging and potential new indications. Diabetes Obes Metab 2024; 26 Suppl 3:31-41. [PMID: 38965738 DOI: 10.1111/dom.15756] [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: 04/05/2024] [Revised: 06/16/2024] [Accepted: 06/16/2024] [Indexed: 07/06/2024]
Abstract
Metformin is best known as a foundational therapy for type 2 diabetes but is also used in other contexts in clinical medicine with a number of emerging and potential indications. Many of its beneficial effects may be mediated by modest effects on weight loss and insulin sensitivity, but it has multiple other known mechanisms of action. Current clinical uses beyond type 2 diabetes include: polycystic ovarian syndrome; diabetes in pregnancy/gestational diabetes; prevention of type 2 diabetes in prediabetes; and adjunct therapy in type 1 diabetes. As metformin has been in clinical use for almost 70 years, much of the underpinning evidence for its use in these conditions is, by definition, based on trials conducted before the advent of contemporary evidence-based medicine. As a result, some of the above-established uses are 'off-label' in many regulatory territories and their use varies accordingly in different countries. Going forward, several current 'repurposing' investigational uses of metformin are also being investigated: prevention of cancer (including in Li Fraumeni syndrome), renal protection, Alzheimer's disease, metabolic dysfunction-associated steatotic liver disease and promotion of healthy ageing. Despite the longevity of metformin and its important current roles beyond type 2 diabetes in clinical medicine, it has further potential and much research is ongoing.
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Affiliation(s)
- John R Petrie
- School of Health and Wellbeing, University of Glasgow, Glasgow, UK
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2
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Zheng Q, Zhao J, Yuan J, Qin Y, Zhu Z, Liu J, Sun S. Delaying Renal Aging: Metformin Holds Promise as a Potential Treatment. Aging Dis 2024; 16:1397-1413. [PMID: 39012670 PMCID: PMC12096913 DOI: 10.14336/ad.2024.0168] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2024] [Accepted: 06/06/2024] [Indexed: 07/17/2024] Open
Abstract
Given the rapid aging of the population, age-related diseases have become an excessive burden on global health care. The kidney, a crucial metabolic organ, ages relatively quickly. While the aging process itself does not directly cause kidney damage, the physiological changes that accompany it can impair the kidney's capacity for self-repair. This makes aging kidneys more susceptible to diseases, including increased risks of chronic kidney disease and end-stage renal disease. Therefore, delaying the progression of renal aging and preserving the youthful vitality of the kidney are crucial for preventing kidney diseases. However, effective strategies against renal aging are still lacking due to the underlying mechanisms of renal aging, which have not been fully elucidated. Accumulating evidence suggests that metformin has beneficial effects in mitigating renal aging. Metformin has shown promising anti-aging results in animal models but has not been tested for this purpose yet in clinical trials. These findings indicate the potential of metformin as an anti-renal aging drug. In this review, we primarily discuss the characteristics and mechanisms of kidney aging and the potential effects of metformin against renal aging.
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Affiliation(s)
- Qiao Zheng
- Department of Postgraduate Student, Xi’an Medical University, Xi’an, China
- Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi’an, China
| | - Jin Zhao
- Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi’an, China
| | - Jinguo Yuan
- Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi’an, China
| | - Yunlong Qin
- Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi’an, China
| | - Zhanxin Zhu
- Department of Postgraduate Student, Xi’an Medical University, Xi’an, China
- Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi’an, China
| | - Jie Liu
- Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi’an, China
| | - Shiren Sun
- Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi’an, China
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Li M, Liu L, Zhang C, Deng L, Zhong Y, Liao B, Li X, Wan Y, Feng J. The latest emerging drugs for the treatment of diabetic cardiomyopathy. Expert Opin Pharmacother 2024; 25:641-654. [PMID: 38660817 DOI: 10.1080/14656566.2024.2347468] [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: 02/05/2024] [Accepted: 04/22/2024] [Indexed: 04/26/2024]
Abstract
INTRODUCTION Diabetic cardiomyopathy (DCM) is a serious complication of diabetes mellitus involving multiple pathophysiologic mechanisms. In addition to hypoglycemic agents commonly used in diabetes, metabolism-related drugs, natural plant extracts, melatonin, exosomes, and rennin-angiotensin-aldosterone system are cardioprotective in DCM. However, there is a lack of systematic summarization of drugs for DCM. AREAS COVERED In this review, the authors systematically summarize the most recent drugs used for the treatment of DCM and discusses them from the perspective of DCM pathophysiological mechanisms. EXPERT OPINION We discuss DCM drugs from the perspective of the pathophysiological mechanisms of DCM, mainly including inflammation and metabolism. As a disease with multiple pathophysiological mechanisms, the combination of drugs may be more advantageous, and we have discussed some of the current studies on the combination of drugs.
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Affiliation(s)
- Minghao Li
- Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Key Laboratory of Medical Electrophysiology, Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, China
| | - Lin Liu
- Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Key Laboratory of Medical Electrophysiology, Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, China
| | - Chunyu Zhang
- Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Key Laboratory of Medical Electrophysiology, Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, China
| | - Li Deng
- Department of Rheumatology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Yi Zhong
- Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Key Laboratory of Medical Electrophysiology, Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, China
| | - Bin Liao
- Department of Cardiovascular Surgery, Metabolic Vascular Diseases Key Laboratory of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Xiuying Li
- Department of Pharmacy, The Affiliated Hospital of Southwest Medical University; Department of Pathophysiology, School of Basic Medical Science, Southwest Medical University, Luzhou, China
| | - Ying Wan
- Department of Pharmacy, The Affiliated Hospital of Southwest Medical University; Department of Pathophysiology, School of Basic Medical Science, Southwest Medical University, Luzhou, China
| | - Jian Feng
- Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Key Laboratory of Medical Electrophysiology, Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, China
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Zhang GH, Liu H, Liu MH, Liu YC, Wang JQ, Wang Y, Wang X, Xiang Z, Liu W. Network Toxicology Prediction and Molecular Docking-based Strategy to Explore the Potential Toxicity Mechanism of Metformin Chlorination Byproducts in Drinking Water. Comb Chem High Throughput Screen 2024; 27:101-117. [PMID: 37170985 DOI: 10.2174/1386207326666230426105412] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Revised: 12/26/2022] [Accepted: 01/13/2023] [Indexed: 05/13/2023]
Abstract
BACKGROUND Metformin (MET), a worldwide used drug for treating type 2 diabetes but not metabolized by humans, has been found with the largest amount in the aquatic environment. Two MET chlorination byproducts, including Y and C, were transformed into drinking water during chlorination. However, the potential toxicity of the byproducts in hepatotoxicity and reproduction toxicity remains unclear. METHODS The TOPKAT database predicted the toxicological properties of metformin disinfection by-products. The targets of metformin disinfection by-products were mainly obtained from the PharmMapper database, and then the targets of hepatotoxicity and reproductive toxicity were screened from GeneCards. The overlapping targets of toxic component targets and the hepatotoxicity or reproduction toxicity targets were regarded as the key targets. Then, the STRING database analyzed the key target to construct a protein-protein interaction network (PPI) and GO, and KEGG analysis was performed by the DAVID platform. Meanwhile, the PPI network and compound- target network were constructed by Cytoscape 3.9.1. Finally, Discovery Studio 2019 software was used for molecular docking verification of the two toxic compounds and the core genes. RESULTS Y and C exhibited hepatotoxicity, carcinogenicity, and mutagenicity evaluated by TOPKAT. There were 22 potential targets relating to compound Y and hepatotoxicity and reproduction toxicity and 14 potential targets relating to compound C and hepatotoxicity and reproduction toxicity. PPI network analysis showed that SRC, MAPK14, F2, PTPN1, IL2, MMP3, HRAS, and RARA might be the key targets; the KEGG analysis indicated that compounds Y and C caused hepatotoxicity through Hepatitis B, Pathways in cancer, Chemical carcinogenesis-reactive oxygen species, Epstein-Barr virus infection; compound Y and C caused reproduction toxicity through GnRH signaling pathway, Endocrine resistance, Prostate cancer, Progesterone-mediated oocyte maturation. Molecular docking results showed that 2 compounds could fit in the binding pocket of the 7 hub genes. CONCLUSION This study preliminarily revealed the potential toxicity and possible toxicity mechanism of metformin disinfection by-products and provided a new idea for follow-up research.
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Affiliation(s)
- Gui-Hong Zhang
- School of Pharmaceutical Science, Liaoning University, Shenyang, 110000, China
| | - Hongwei Liu
- Department of Head and Neck Surgery, Cancer Hospital of China Medical University, Shenyang 110042, China
| | - Mei-Hua Liu
- School of Pharmaceutical Science, Liaoning University, Shenyang, 110000, China
| | - Yang-Cheng Liu
- School of Pharmaceutical Science, Liaoning University, Shenyang, 110000, China
| | - Jia-Qi Wang
- School of Pharmaceutical Science, Liaoning University, Shenyang, 110000, China
| | - Yang Wang
- School of Pharmaceutical Science, Liaoning University, Shenyang, 110000, China
| | - Xin Wang
- School of Pharmaceutical Science, Liaoning University, Shenyang, 110000, China
| | - Zheng Xiang
- School of Pharmaceutical Science, Liaoning University, Shenyang, 110000, China
| | - Wei Liu
- School of Pharmaceutical Science, Liaoning University, Shenyang, 110000, China
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Raoofi S, Pashazadeh Kan F, Rafiei S, Hoseinipalangi Z, Rezaei S, Ahmadi S, Masoumi M, Noorani Mejareh Z, Roohravan Benis M, Sharifi A, Shabaninejad H, Kiaee ZM, Ghashghaee A. Hemodialysis and peritoneal dialysis-health-related quality of life: systematic review plus meta-analysis. BMJ Support Palliat Care 2023; 13:365-373. [PMID: 34301643 DOI: 10.1136/bmjspcare-2021-003182] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Accepted: 07/08/2021] [Indexed: 01/11/2023]
Abstract
BACKGROUND Patients with end-stage renal disease undergoing haemodialysis experience a variety of stressors leading to decreased level of quality of life (QoL). Thus, in this study, we aimed to review the current literature and identify factors affecting the health-related QoL (HRQoL) in these patients. METHODS A total of 147 studies were extracted from databases of Web of Science, PubMed, Scopus, Google Scholar, and Embase published between January 2000 and December 2020. Data were analysed using R software and results were reported with reference to Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards. RESULTS A total of 623 728 patients undergoing dialysis participated in 147 studies in which QoL was assessed by means of two valid questionnaires, including Short-Form 36 (SF-36) and Kidney Disease Quality of Life (KDQOL)-short form V.1.3. Total HRQoL score for patients undergoing dialysis measured by KDQOL was 64.25 (95% CI 55.67 to 72.82). Based on SF-36, the mean score of mental health items was higher than the mean score of physical health condition. Furthermore, meta-regression based on the geographical place of residence revealed that the highest QoL in patients was observed in Japan, 66.96 (95% CI 63.65 to 70.28) and Brazil, 58.03 (95% CI 53.45 to 62.6). CONCLUSION Studies conducted on HRQoL among patients undergoing dialysis recommend useful strategies to clinicians, letting them assess patients' QoL in terms of a wide range of physical, mental and environmental aspects.
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Affiliation(s)
- Samira Raoofi
- Student Research Committee, School of Health Management and Information Sciences, Iran University of Medical Sciences, Tehran, Iran (the Islamic Republic of)
| | - Fatemeh Pashazadeh Kan
- Health Management and Economics Research Center, Health Management Research Institute, Iran University of Medical Sciences, Tehran, Iran
| | - Sima Rafiei
- Social Determinants of Health Research Center, Qazvin University of Medical Sciences, Qazvin, Iran (the Islamic Republic of)
| | - Zahra Hoseinipalangi
- Student Research Committee, School of Nursing and Midwifery, Iran University of Medical Sciences, Tehran, Iran (the Islamic Republic of)
| | - Sepide Rezaei
- Student Research Committee, School of Health Management and Information Sciences, Iran University of Medical Sciences, Tehran, Iran (the Islamic Republic of)
| | - Saba Ahmadi
- Student Research Committee, School of Nursing and Midwifery, Iran University of Medical Sciences, Tehran, Iran (the Islamic Republic of)
| | - Maryam Masoumi
- Clinical Research and Development Center, Qom University of Medical Sciences, Qom, Iran
| | - Zahra Noorani Mejareh
- Student Research Committee, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Mahshid Roohravan Benis
- Student Research Committee, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Alireza Sharifi
- Student Research Committee, Qom University of Medical Sciences, Qom, Tehran, Iran (the Islamic Republic of)
| | - Hosein Shabaninejad
- Population Health Sciences Institute (PHSI), Newcastle University, Newcastle, UK
| | | | - Ahmad Ghashghaee
- Student Research Center, Qazvin university of medical sciences, Qazvin, Iran
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Zhang M, Li H, Huang L, Liu Y, Jiao XF, Zeng L, Jia ZJ, Cheng G, Zhang L, Zhang W. Drug-associated kidney injury in children: a disproportionality analysis of the FDA Adverse Event Reporting System. Eur J Pediatr 2023; 182:4655-4661. [PMID: 37561197 DOI: 10.1007/s00431-023-05146-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Revised: 07/27/2023] [Accepted: 08/01/2023] [Indexed: 08/11/2023]
Abstract
Drug-associated kidney injury is related to longer hospitalization and increased risk of chronic kidney disease and mortality. However, there is currently a lack of large population studies on drug-associated kidney injury in children. This study aimed to study perform data mining to generate hypotheses on drugs, which may deserve to be assessed as per their potential risk of increasing kidney injury in children. We extracted and analyzed reports on drugs associated with kidney injury in children in the FDA Adverse Event Reporting System (FAERS). We conducted a disproportionality analysis using proportional reporting ratio (PRR) to evaluate the association between drugs and kidney injury in children. Meanwhile, comparisons were performed with drug labels to identify drugs that, despite not having kidney injury currently mentioned in their labels, may potentially be associated with risks of kidney injury in children. A total of 6347 children had drug-associated kidney injury in the FAERS database. The top five drugs with the highest PRR were gentamicin (PRR = 12.28, N = 157 cases, Chi-Squared = 1602.77), piperacillin-tazobactam (PRR = 9.77, N = 129 cases, Chi-Squared = 1003.24), amlodipine (PRR = 8.98, N = 271 cases, Chi-Squared = 1861.46), vancomycin (PRR = 8.91, N = 295 cases, Chi-Squared = 1998.64), and ceftriaxone (PRR = 8.00, N = 251 cases, Chi-Squared = 1494.02). According to drug labels, 9 drugs (9/30) were classified as potential nephrotoxins. CONCLUSIONS Approximately one-third of drugs associated with kidney injury in children do not list kidney injury as a side effect in their drug labels. Future studies are therefore warranted to evaluate whether these drugs are associated with such a risk. WHAT IS KNOWN • Nephrotoxic drugs are an increasingly common cause of acute kidney injury in hospitalized children. • Currently, no study has systematically combed drugs associated with kidney injury in children. WHAT IS NEW • Approximately a third of drugs showing signals for potential kidney injury in children in data mining do not mention this side effect in their drug labels. • This study provides data on drugs needing further study to determine whether they might increase the risk of kidney injury in children.
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Affiliation(s)
- Miao Zhang
- Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, China
- Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, China
- NMPA Key Laboratory for Technical Research On Drug Products In Vitro and In Vivo Correlation, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, China
- West China School of Pharmacy, Sichuan University, Chengdu, China
| | - Hailong Li
- Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, China
- Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, China
- NMPA Key Laboratory for Technical Research On Drug Products In Vitro and In Vivo Correlation, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, China
| | - Liang Huang
- Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, China
- Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, China
- NMPA Key Laboratory for Technical Research On Drug Products In Vitro and In Vivo Correlation, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, China
| | - Yan Liu
- Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, China
- Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, China
- NMPA Key Laboratory for Technical Research On Drug Products In Vitro and In Vivo Correlation, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, China
- West China School of Pharmacy, Sichuan University, Chengdu, China
| | - Xue-Feng Jiao
- Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, China
- Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, China
- NMPA Key Laboratory for Technical Research On Drug Products In Vitro and In Vivo Correlation, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, China
| | - Linan Zeng
- Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, China
- Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, China
- NMPA Key Laboratory for Technical Research On Drug Products In Vitro and In Vivo Correlation, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, China
| | - Zhi-Jun Jia
- Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, China
- Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, China
- NMPA Key Laboratory for Technical Research On Drug Products In Vitro and In Vivo Correlation, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, China
- West China School of Pharmacy, Sichuan University, Chengdu, China
| | - Guo Cheng
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, China
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China
- Laboratory of Molecular Translational Medicine, Center for Translational Medicine, Sichuan University, Chengdu, China
| | - Lingli Zhang
- West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China.
- Medical Big Data Center, Sichuan University, Chengdu, China.
| | - Wei Zhang
- Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, China.
- Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, China.
- NMPA Key Laboratory for Technical Research On Drug Products In Vitro and In Vivo Correlation, Chengdu, China.
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, China.
- Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, Chengdu, China.
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Peng W, Yang B, Qiao H, Liu Y, Lin Y. Metformin use is associated with reduced acute kidney injury following coronary artery bypass grafting in patients with type 2 diabetes: An inverse probability of treatment weighting analysis. Pharmacotherapy 2023; 43:778-786. [PMID: 37199291 DOI: 10.1002/phar.2827] [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: 02/18/2023] [Revised: 03/26/2023] [Accepted: 03/30/2023] [Indexed: 05/19/2023]
Abstract
STUDY OBJECTIVE Acute kidney injury (AKI) is a common and serious complication after coronary artery bypass grafting (CABG) surgery. Patients with diabetes are commonly associated with renal microvascular complications and have a greater risk of AKI after CABG surgery. This study aimed to explore whether preoperative metformin administration could reduce the incidence of postoperative AKI following CABG in patients with type 2 diabetes. DESIGN Patients with diabetes who underwent CABG were retrospectively included in this study. AKI after CABG was defined according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. The effects of metformin on postoperative AKI following CABG in patients were compared and analyzed. DATA SOURCE Patients were enrolled in this study between January 2019 and December 2020 in Beijing Anzhen Hospital. PATIENTS A total of 812 patients were enrolled. The patients were divided into the metformin group (203 cases) and the control group (609 cases) according to whether metformin was used preoperatively. INTERVENTION Inverse probability of treatment weighting (IPTW) was applied to minimize baseline differences between the two groups. IPT-weighted p values were analyzed to evaluate the postoperative outcomes between the two groups. MEASUREMENTS AND MAIN RESULTS The incidence of AKI in the metformin group and the control group was compared. After IPTW adjustment, the incidence of AKI in the metformin group was lower than the control group (IPTW-adjusted p < 0.001). In the subgroup analysis, metformin showed significant protective effects in the estimated glomerular filtration rate (eGFR) < 60 mL/min per 1.73 m2 and eGFR 60-90 mL/min per 1.73 m2 subgroups, which was not observed in the eGFR ≥90 mL/min per 1.73 m2 subgroup. No significant differences in the incidence of renal replacement therapy, reoperation due to bleeding, in-hospital mortality, or red blood cell transfusion volume were observed between the two groups. CONCLUSIONS In this study, we provided evidence that preoperative metformin was associated with a significant reduction of postoperative AKI following CABG in patients with diabetes. Metformin showed significant protective effects in patients with mild-to-moderate renal insufficiency.
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Affiliation(s)
- Wenxing Peng
- Department of Pharmacy, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Bo Yang
- Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Huanyu Qiao
- Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Yongmin Liu
- Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Yang Lin
- Department of Pharmacy, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
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8
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Anderson NE, Kyte D, McMullan C, Cockwell P, Aiyegbusi OL, Verdi R, Calvert M. Global use of electronic patient-reported outcome systems in nephrology: a mixed methods study. BMJ Open 2023; 13:e070927. [PMID: 37438075 DOI: 10.1136/bmjopen-2022-070927] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/14/2023] Open
Abstract
OBJECTIVES The use of electronic patient-reported outcome (ePRO) systems to support the management of patients with chronic kidney disease is increasing. This mixed-methods study aimed to comprehensively identify existing and developing ePRO systems, used in nephrology settings globally, ascertaining key characteristics and factors for successful implementation. STUDY DESIGN ePRO systems and developers were identified through a scoping review of the literature and contact with field experts. Developers were invited to participate in a structured survey, to summarise key system characteristics including: (1) system objectives, (2) population, (3) PRO measures used, (4) level of automation, (5) reporting, (6) integration into workflow and (7) links to electronic health records/national registries. Subsequent semistructured interviews were conducted to explore responses. SETTING AND PARTICIPANTS Eligible systems included those being developed or used in nephrology settings to assess ePROs and summarise results to care providers. System developers included those with a key responsibility for aspects of the design, development or implementation of an eligible system. ANALYTICAL APPROACH Structured survey data were summarised using descriptive statistics. Interview transcripts were analysed using Codebook Thematic Analysis using domains from the Consolidated Framework for Implementation Research. RESULTS Fifteen unique ePRO systems were identified across seven countries; 10 system developers completed the structured survey and 7 participated in semistructured interviews. Despite system heterogeneity, reported features required for effective implementation included early and sustained patient involvement, clinician champions and expanding existing electronic platforms to integrate ePROs. Systems demonstrated several common features, with the majority being implemented within research settings, thereby affecting system implementation readiness for real-world application. CONCLUSIONS There has been considerable research investment in ePRO systems. The findings of this study outline key system features and factors to support the successful implementation of ePROs in routine kidney care.Cite Now.
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Affiliation(s)
- Nicola Elizabeth Anderson
- Institute of Applied Heath Research, Centre for Patient Reported Outcomes Research, University of Birmingham, Birmingham, UK
- Research, Development and Innovation, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
- NIHR Applied Research Collaboration, West Midlands, University of Birmingham, Birmingham, UK
| | - Derek Kyte
- Institute of Applied Heath Research, Centre for Patient Reported Outcomes Research, University of Birmingham, Birmingham, UK
- School of Allied Health and Community, University of Worcester, Worcester, UK
| | - Christel McMullan
- Institute of Applied Heath Research, Centre for Patient Reported Outcomes Research, University of Birmingham, Birmingham, UK
- NIHR SRMRC, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, UK
- NIHR Blood and Transplant Research Unit (BTRU) in Precision Transplant and Cellular Therapeutics, University of Birmingham, Birmingham, UK
| | - Paul Cockwell
- Institute of Applied Heath Research, Centre for Patient Reported Outcomes Research, University of Birmingham, Birmingham, UK
- Department of Renal Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Olalekan Lee Aiyegbusi
- Institute of Applied Heath Research, Centre for Patient Reported Outcomes Research, University of Birmingham, Birmingham, UK
- NIHR Applied Research Collaboration, West Midlands, University of Birmingham, Birmingham, UK
- NIHR Blood and Transplant Research Unit (BTRU) in Precision Transplant and Cellular Therapeutics, University of Birmingham, Birmingham, UK
- NIHR Birmingham Biomedical Research Centre, University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, University of Birmingham, Birmingham, UK
- Birmingham Health Partners Centre for Regulatory Science and Innovation, University of Birmingham, Birmingham, UK
| | - Rav Verdi
- Patient Partner, Institute of Applied Health Research,Centre for Patient-Reported Outcomes Research (CPROR), University of Birmingham, Birmingham, UK
| | - Melanie Calvert
- Institute of Applied Heath Research, Centre for Patient Reported Outcomes Research, University of Birmingham, Birmingham, UK
- NIHR Applied Research Collaboration, West Midlands, University of Birmingham, Birmingham, UK
- NIHR SRMRC, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, UK
- NIHR Blood and Transplant Research Unit (BTRU) in Precision Transplant and Cellular Therapeutics, University of Birmingham, Birmingham, UK
- NIHR Birmingham Biomedical Research Centre, University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, University of Birmingham, Birmingham, UK
- Birmingham Health Partners Centre for Regulatory Science and Innovation, University of Birmingham, Birmingham, UK
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9
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Scilletta S, Di Marco M, Miano N, Filippello A, Di Mauro S, Scamporrino A, Musmeci M, Coppolino G, Di Giacomo Barbagallo F, Bosco G, Scicali R, Piro S, Purrello F, Di Pino A. Update on Diabetic Kidney Disease (DKD): Focus on Non-Albuminuric DKD and Cardiovascular Risk. Biomolecules 2023; 13:biom13050752. [PMID: 37238622 DOI: 10.3390/biom13050752] [Citation(s) in RCA: 36] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 04/25/2023] [Accepted: 04/25/2023] [Indexed: 05/28/2023] Open
Abstract
The classic description of diabetic kidney disease (DKD) involves progressive stages of glomerular hyperfiltration, microalbuminuria, proteinuria, and a decline in the estimated glomerular filtration rate (eGFR), leading to dialysis. In recent years, this concept has been increasingly challenged as evidence suggests that DKD presents more heterogeneously. Large studies have revealed that eGFR decline may also occur independently from the development of albuminuria. This concept led to the identification of a new DKD phenotype: non-albuminuric DKD (eGFR < 60 mL/min/1.73 m2, absence of albuminuria), whose pathogenesis is still unknown. However, various hypotheses have been formulated, the most likely of which is the acute kidney injury-to-chronic kidney disease (CKD) transition, with prevalent tubular, rather than glomerular, damage (typically described in albuminuric DKD). Moreover, it is still debated which phenotype is associated with a higher cardiovascular risk, due to contrasting results available in the literature. Finally, much evidence has accumulated on the various classes of drugs with beneficial effects on DKD; however, there is a lack of studies analyzing the different effects of drugs on the various phenotypes of DKD. For this reason, there are still no specific guidelines for therapy in one phenotype rather than the other, generically referring to diabetic patients with CKD.
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Affiliation(s)
- Sabrina Scilletta
- Department of Clinical and Experimental Medicine, University of Catania, 95122 Catania, Italy
| | - Maurizio Di Marco
- Department of Clinical and Experimental Medicine, University of Catania, 95122 Catania, Italy
| | - Nicoletta Miano
- Department of Clinical and Experimental Medicine, University of Catania, 95122 Catania, Italy
| | - Agnese Filippello
- Department of Clinical and Experimental Medicine, University of Catania, 95122 Catania, Italy
| | - Stefania Di Mauro
- Department of Clinical and Experimental Medicine, University of Catania, 95122 Catania, Italy
| | - Alessandra Scamporrino
- Department of Clinical and Experimental Medicine, University of Catania, 95122 Catania, Italy
| | - Marco Musmeci
- Department of Clinical and Experimental Medicine, University of Catania, 95122 Catania, Italy
| | - Giuseppe Coppolino
- Department of Clinical and Experimental Medicine, University of Catania, 95122 Catania, Italy
| | | | - Giosiana Bosco
- Department of Clinical and Experimental Medicine, University of Catania, 95122 Catania, Italy
| | - Roberto Scicali
- Department of Clinical and Experimental Medicine, University of Catania, 95122 Catania, Italy
| | - Salvatore Piro
- Department of Clinical and Experimental Medicine, University of Catania, 95122 Catania, Italy
| | - Francesco Purrello
- Department of Clinical and Experimental Medicine, University of Catania, 95122 Catania, Italy
| | - Antonino Di Pino
- Department of Clinical and Experimental Medicine, University of Catania, 95122 Catania, Italy
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10
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Shchepalina A, Chebotareva N, Akulkina L, Brovko M, Sholomova V, Androsova T, Korotchaeva Y, Kalmykova D, Tanaschuk E, Taranova M, Lebedeva M, Beketov V, Moiseev S. Acute Kidney Injury in Hospitalized Patients with COVID-19: Risk Factors and Serum Biomarkers. Biomedicines 2023; 11:biomedicines11051246. [PMID: 37238917 DOI: 10.3390/biomedicines11051246] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Revised: 04/16/2023] [Accepted: 04/18/2023] [Indexed: 05/28/2023] Open
Abstract
BACKGROUND AKI is one of the COVID-19 complications with high prognostic significance. In our research, we studied the prognostic role of several biomarkers that could help us understand AKI pathogenesis in patients with COVID-19. METHODS We evaluated the medical data of 500 patients hospitalized with COVID-19 in Tareev Clinic from 5 October 2020 to 1 March 2022. The diagnosis of COVID-19 was confirmed with positive RNA PCR in nasopharyngeal swabs and/or typical radiological findings on CT scans. Kidney function was assessed in accordance with KDIGO criteria. In the selected 89 patients, we evaluated serum levels of angiopoetin-1, KIM-1, MAC, and neutrophil elastase 2 and their prognostic significance. RESULTS The incidence of AKI in our study was 38%. The main risk factors for kidney injury were male sex, cardiovascular diseases, and chronic kidney disease. High serum angiopoetin-1 levels and a decrease in blood lymphocyte count and fibrinogen level also increased the risk of AKI. CONCLUSIONS AKI is an independent risk factor for death in patients with COVID-19. We propose the prognostic model of AKI development, which includes the combination of serum levels of angiopoetin-1 and KIM-1 on admission. Our model can help to prevent AKI development in patients with coronavirus disease.
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Affiliation(s)
- Anastasia Shchepalina
- Tareev Clinic of Internal Diseases, Department of Internal Diseases, Occupational Diseases and Reumatology, Sechenov First Moscow State Medical University, 119435 Moscow, Russia
| | - Natalia Chebotareva
- Tareev Clinic of Internal Diseases, Department of Internal Diseases, Occupational Diseases and Reumatology, Sechenov First Moscow State Medical University, 119435 Moscow, Russia
- Faculty of Fundamental Medicine, Lomonosov Moscow State University, Build. 1, 119991 Moscow, Russia
| | - Larissa Akulkina
- Tareev Clinic of Internal Diseases, Department of Internal Diseases, Occupational Diseases and Reumatology, Sechenov First Moscow State Medical University, 119435 Moscow, Russia
| | - Mikhail Brovko
- Tareev Clinic of Internal Diseases, Department of Internal Diseases, Occupational Diseases and Reumatology, Sechenov First Moscow State Medical University, 119435 Moscow, Russia
| | - Viktoria Sholomova
- Tareev Clinic of Internal Diseases, Department of Internal Diseases, Occupational Diseases and Reumatology, Sechenov First Moscow State Medical University, 119435 Moscow, Russia
| | - Tatiana Androsova
- Tareev Clinic of Internal Diseases, Department of Internal Diseases, Occupational Diseases and Reumatology, Sechenov First Moscow State Medical University, 119435 Moscow, Russia
| | - Yulia Korotchaeva
- Tareev Clinic of Internal Diseases, Department of Internal Diseases, Occupational Diseases and Reumatology, Sechenov First Moscow State Medical University, 119435 Moscow, Russia
| | - Diana Kalmykova
- Department of Nursing, Sechenov First Moscow State Medical University, 119435 Moscow, Russia
| | - Elena Tanaschuk
- Tareev Clinic of Internal Diseases, Department of Internal Diseases, Occupational Diseases and Reumatology, Sechenov First Moscow State Medical University, 119435 Moscow, Russia
| | - Marina Taranova
- Tareev Clinic of Internal Diseases, Department of Internal Diseases, Occupational Diseases and Reumatology, Sechenov First Moscow State Medical University, 119435 Moscow, Russia
| | - Marina Lebedeva
- Tareev Clinic of Internal Diseases, Department of Internal Diseases, Occupational Diseases and Reumatology, Sechenov First Moscow State Medical University, 119435 Moscow, Russia
| | - Vladimir Beketov
- Tareev Clinic of Internal Diseases, Department of Internal Diseases, Occupational Diseases and Reumatology, Sechenov First Moscow State Medical University, 119435 Moscow, Russia
| | - Sergey Moiseev
- Tareev Clinic of Internal Diseases, Department of Internal Diseases, Occupational Diseases and Reumatology, Sechenov First Moscow State Medical University, 119435 Moscow, Russia
- Faculty of Fundamental Medicine, Lomonosov Moscow State University, Build. 1, 119991 Moscow, Russia
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11
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Michaelidou M, Pappachan JM, Jeeyavudeen MS. Management of diabesity: Current concepts. World J Diabetes 2023; 14:396-411. [PMID: 37122433 PMCID: PMC10130896 DOI: 10.4239/wjd.v14.i4.396] [Citation(s) in RCA: 41] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2022] [Revised: 01/15/2023] [Accepted: 03/20/2023] [Indexed: 04/12/2023] Open
Abstract
The global prevalence of obesity is increasing rapidly with an exponential rise in incidence of type 2 diabetes mellitus in recent years. 'Diabesity', the term coined to show the strong interlink between obesity and diabetes, is the direct cons-equence of the obesity pandemic, and poses significant challenges in the management of the disease. Without addressing the clinical and mechanistic complications of obesity such as metabolic-associated fatty liver disease and obstructive sleep apnoea, a rational management algorithm for diabesity cannot be developed. Several classes of anti-diabetic medications including insulins, sulphonylureas, thiazolidinediones and meglitinides are associated with the risk of weight gain and may potentially worsen diabesity. Therefore, appropriate selection of antidiabetic drug regimen is crucial in the medical management of diabesity. The role of non-pharmacological measures such as dietary adjustments, exercise interventions and bariatric procedures should also be emphasised. Unfortunately, the importance of appropriate and optimal management of diabesity is often overlooked by medical professionals when achieving adequate glycemic control which results in inappropriate management of the disease and its complications. This review provides a narrative clinical update on the evidence behind the management of diabesity.
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Affiliation(s)
- Maria Michaelidou
- Department of Endocrinology and Metabolism, Lancashire Teaching Hospitals NHS Trust, Preston PR2 9HT, United Kingdom
| | - Joseph M Pappachan
- Department of Endocrinology and Metabolism, Lancashire Teaching Hospitals NHS Trust, Preston PR2 9HT, United Kingdom
- Faculty of Science, Manchester Metropolitan University, Manchester M15 6BH, United Kingdom
- Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PL, United Kingdom
| | - Mohammad Sadiq Jeeyavudeen
- Department of Endocrinology & Metabolism, University Hospitals of Edinburgh, Edinburgh EH16 4SA, United Kingdom
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12
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Gui Y, Palanza Z, Fu H, Zhou D. Acute kidney injury in diabetes mellitus: Epidemiology, diagnostic, and therapeutic concepts. FASEB J 2023; 37:e22884. [PMID: 36943403 PMCID: PMC10602403 DOI: 10.1096/fj.202201340rr] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Revised: 02/16/2023] [Accepted: 03/08/2023] [Indexed: 03/23/2023]
Abstract
Acute kidney injury (AKI) and diabetes mellitus (DM) are public health problems that cause a high socioeconomic burden worldwide. In recent years, the landscape of AKI etiology has shifted: Emerging evidence has demonstrated that DM is an independent risk factor for the onset of AKI, while an alternative perspective considers AKI as a bona fide complication of DM. Therefore, it is necessary to systematically characterize the features of AKI in DM. In this review, we summarized the epidemiology of AKI in DM. While focusing on circulation- and tissue-specific microenvironment changes after DM, we described the active cellular and molecular mechanisms of increased kidney susceptibility to AKI under DM stress. We also reviewed the current diagnostic and therapeutic strategies for AKI in DM recommended in the clinic. Updated recognition of the epidemiology, pathophysiology, diagnosis, and medications of AKI in DM is believed to reveal a path to mitigate the frequency of AKI and DM comorbidity that will ultimately improve the quality of life in DM patients.
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Affiliation(s)
- Yuan Gui
- Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, CT, 06030, USA
| | - Zachary Palanza
- Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, CT, 06030, USA
| | - Haiyan Fu
- State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261, USA
| | - Dong Zhou
- Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, CT, 06030, USA
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13
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Metformin as a Potential Antitumor Agent. SERBIAN JOURNAL OF EXPERIMENTAL AND CLINICAL RESEARCH 2022. [DOI: 10.2478/sjecr-2022-0023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Abstract
Some recent findings suggest that metformin, an oral antidiabetic drug, may have antitumor properties. Studies have shown that metformin can alter cell metabolism, both tumor and immune cells, which can greatly influence disease outcome. In this review, we discuss the potential mechanisms in which metformin can directly induce apoptosis of tumor cells as well as mechanisms in which metformin can elicit or enhance antitumor immune response.
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14
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Wang H, Lambourg E, Guthrie B, Morales DR, Donnan PT, Bell S. Patient outcomes following AKI and AKD: a population-based cohort study. BMC Med 2022; 20:229. [PMID: 35854309 PMCID: PMC9297625 DOI: 10.1186/s12916-022-02428-8] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Accepted: 06/06/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Acute kidney injury (AKI) is common and associated with adverse outcomes as well as important healthcare costs. However, evidence examining the epidemiology of acute kidney disease (AKD)-recently defined as AKI persisting between 7 and 90 days-remains limited. The aims of this study were to establish the rates of early AKI recovery, progression to AKD and non-recovery; examine risk factors associated with non-recovery and investigate the association between recovery timing and adverse outcomes, in a population-based cohort. METHODS All adult residents of Tayside & Fife, Scotland, UK, with at least one episode of community or hospital-managed AKI using KDIGO creatinine-based definition during the period 1 January 2010 to 31 December 2018 were identified. Logistic regression was used to examine factors associated with non-recovery, and Cox modelling was used to establish associations between AKI recovery timing and risks of mortality and development of de novo CKD. RESULTS Over 9 years, 56,906 patients with at least one AKI episode were identified with 18,773 (33%) of these progressing to AKD. Of those progressing to AKD, 5059 (27%) had still not recovered at day 90 post AKI diagnosis. Risk factors for AKD included: increasing AKI severity, pre-existing cancer or chronic heart failure and recent use of loop diuretics. Compared with early AKI recovery, progression to AKD was associated with increased hazard of 1-year mortality and de novo CKD (HR = 1.20, 95% CI 1.13 to 1.26 and HR = 2.21, 95% CI 1.91 to 2.57 respectively). CONCLUSIONS These findings highlight the importance of early AKI recognition and management to avoid progression to AKD and long-term adverse outcomes.
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Affiliation(s)
- Huan Wang
- Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, DD1 9SY, UK
| | - Emilie Lambourg
- Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, DD1 9SY, UK
| | - Bruce Guthrie
- Advanced Care Research Centre, Usher Institute of Population Health Sciences and Informatics, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK
| | - Daniel R Morales
- Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, DD1 9SY, UK.,Department of Public Health, University of Southern Denmark, Odense, Denmark
| | - Peter T Donnan
- Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, DD1 9SY, UK
| | - Samira Bell
- Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, DD1 9SY, UK. .,Renal Unit, Ninewells Hospital, Dundee, UK.
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15
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Sachan A, Nayyar R, Kumar A, Rewari V. Postoperative dengue haemorrhagic shock and Trichosporon fungal sepsis: a multidisciplinary rescue. BMJ Case Rep 2022; 15:e249814. [PMID: 35790323 PMCID: PMC9258485 DOI: 10.1136/bcr-2022-249814] [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] [Accepted: 06/20/2022] [Indexed: 11/04/2022] Open
Abstract
A woman in her 30s had robotic pyeloplasty done for right ureteropelvic junction obstruction. Incidentally she developed dengue viral fever starting on postoperative day 1 itself, which progressed to dengue haemorrhagic shock by 1 week, complicating pyeloplasty due to pelvicalyceal haematoma. Dengue associated shock was superimposed with subsequent gram-negative bacterial sepsis, further complicated later with Trichosporon fungal sepsis. She was managed under multidisciplinary care, involving urology, infectious disease and ICU care. Her diagnostic and difficult management issues due to these rare sequential medical issues in an otherwise usually uncomplicated postsurgical phase are discussed along with short review of literature. This case highlights the importance of early diagnosis, timely supportive care and appropriate management in such tropical infections with significant associated mortality.
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Affiliation(s)
- Ankit Sachan
- Urology, All India Institute of Medical Sciences, New Delhi, Delhi, India
| | - Rishi Nayyar
- Urology, All India Institute of Medical Sciences, New Delhi, Delhi, India
| | - Arvind Kumar
- Medicine, All India Institute of Medical Sciences, New Delhi, Delhi, India
| | - Vimi Rewari
- Anaesthesiology, Pain Medicine and Critical Care, All India Institute of Medical Sciences, New Delhi, India
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16
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Tshimologo M, Allen K, Coyle D, Damery S, Dikomitis L, Fotheringham J, Hill H, Lambie M, Phillips-Darby L, Solis-Trapala I, Williams I, Davies SJ. Intervening to eliminate the centre-effect variation in home dialysis use: protocol for Inter-CEPt-a sequential mixed-methods study designing an intervention bundle. BMJ Open 2022; 12:e060922. [PMID: 35676002 PMCID: PMC9189878 DOI: 10.1136/bmjopen-2022-060922] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Accepted: 04/28/2022] [Indexed: 12/03/2022] Open
Abstract
INTRODUCTION Use of home dialysis by centres in the UK varies considerably and is decreasing despite attempts to encourage greater use. Knowing what drives this unwarranted variation requires in-depth understanding of centre cultural and organisational factors and how these relate to quantifiable centre performance, accounting for competing treatment options. This knowledge will be used to identify components of a practical and feasible intervention bundle ensuring this is realistic and cost-effective. METHODS AND ANALYSIS Underpinned by the non-adoption, abandonment, scale-up, spread and sustainability framework, our research will use an exploratory sequential mixed-methods approach. Insights from multisited focused team ethnographic and qualitative research at four case study sites will inform development of a national survey of 52 centres. Survey results, linked to patient-level data from the UK Renal Registry, will populate a causal graph describing patient and centre-level factors, leading to uptake of home dialysis and multistate models incorporating patient-level treatment modality history and mortality. This will inform a contemporary economic evaluation of modality cost-effectiveness that will quantify how modification of factors facilitating home dialysis, identified from the ethnography and survey, might yield the greatest improvements in costs, quality of life and numbers on home therapies. Selected from these factors, using the capability, opportunity and motivation for behaviour change framework (COM-B) for intervention design, the optimal intervention bundle will be developed through workshops with patients and healthcare professionals to ensure acceptability and feasibility. Patient and public engagement and involvement is embedded throughout the project. ETHICS AND DISSEMINATION Ethics approval has been granted by the Health Research Authority reference 20-WA-0249. The intervention bundle will comprise components for all stake holder groups: commissioners, provider units, recipients of dialysis, their caregivers and families. To reache all these groups, a variety of knowledge exchange methods will be used: short guides, infographics, case studies, National Institute for Health and Care Excellence guidelines, patient conferences, 'Getting it Right First Time' initiative, Clinical Reference Group (dialysis).
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Affiliation(s)
- Maatla Tshimologo
- Renal Research Group, School of Medicine, Keele University, Keele, UK
| | - Kerry Allen
- Health Services Management Centre, University of Birmingham, Birmingham, UK
| | - David Coyle
- NIHR Devices for Dignity MedTech Co-operative, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - Sarah Damery
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Lisa Dikomitis
- Renal Research Group, School of Medicine, Keele University, Keele, UK
- Kent and Medway Medical School, University of Kent, Canterbury, UK
| | - James Fotheringham
- School of Health and Related Research, University of Sheffield, Sheffield, UK
| | - Harry Hill
- School of Health and Related Research, University of Sheffield, Sheffield, UK
| | - Mark Lambie
- Renal Research Group, School of Medicine, Keele University, Keele, UK
| | | | | | - Iestyn Williams
- Health Services Management Centre, University of Birmingham, Birmingham, UK
| | - Simon J Davies
- Renal Research Group, School of Medicine, Keele University, Keele, UK
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17
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Hajsadeghi S, Gholizadeh Mesgarha M, Pour Mohammad A, Saberi Shahrbabaki A, Talebi A. A concealed history behind the disaster: Extremely rare presentations of metformin toxicity in a patient with body dysmorphic disorder. Toxicol Rep 2022; 9:848-851. [PMID: 36561946 PMCID: PMC9764204 DOI: 10.1016/j.toxrep.2022.04.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Revised: 04/10/2022] [Accepted: 04/11/2022] [Indexed: 12/25/2022] Open
Abstract
Metformin is a widely used anti-hyperglycemic agent with weight loss effect properties but besides its various utilities, despite being very rare, it has its characteristic toxicity and adverse effects when used in large doses and for the long-term or in patients with renal impairment. We presented here a case of a 36-year-old woman who developed several presentations with diverse features during three years comprising neuropathic symptoms, severe lactic acidosis, three episodes of cardiogenic shock, acute kidney injury, megaloblastic anemia, pancytopenia, and hyponatremia and did not receive a definite diagnosis after each presentation until when she inadvertently disclosed her abuse of extremely unusual doses of metformin during these three years with aim of weight reduction obsessively without knowing that her symptoms could pertain to metformin overdose. She was eventually diagnosed with a body dysmorphic disorder which led to unreasonable abuse of metformin pills that consequently caused its toxicity. Thereafter, with cease of metformin use and psychiatric treatment, her symptoms did not recur and she was doing well after one year of her last admission. Based on the review of the literature, this is the first case of metformin toxicity in a patient with body dysmorphic disorder who was affected with extremely rare features of this intoxication, nevertheless, every manifestation of the patient was discussed exhaustively according to the current and available medical literature.
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Affiliation(s)
- Shokoufeh Hajsadeghi
- Research center for prevention of cardiovascular disease, Institute of endocrinology & metabolism, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | - Milad Gholizadeh Mesgarha
- Faculty of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran,Correspondence to: Rasool-E-Akram Medical Center, Niayesh St., Sattarkhan Ave., Tehran 1445613131, Iran.
| | - Arash Pour Mohammad
- Faculty of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | | | - Aisa Talebi
- Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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18
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Andersson A, Hansson E, Ekström U, Grubb A, Abrahamson M, Jakobsson K, Xu Y. Large difference but high correlation between creatinine and cystatin C estimated glomerular filtration rate in Mesoamerican sugarcane cutters. Occup Environ Med 2022; 79:497-502. [PMID: 35354651 PMCID: PMC9209661 DOI: 10.1136/oemed-2021-107990] [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: 09/03/2021] [Accepted: 03/06/2022] [Indexed: 11/04/2022]
Abstract
OBJECTIVES To explore the relationship between creatinine and cystatin C based estimated glomerular filtration rate (eGFR) in actively working sugarcane cutters. METHODS This cohort study included 458 sugarcane cutters from Nicaragua and El Salvador. Serum samples were taken before and at end of harvest seasons and analysed for creatinine and cystatin C. Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas were used to calculate eGFRs based on creatinine (eGFRcr), cystatin C (eGFRcys) and both creatinine and cystatin C (eGFRcrcys) at each time point. Bland-Altman plots and paired t-tests were used to compare the difference between eGFRcr and eGFRcys, and the difference in eGFRs between before and at end of the harvest seasons. RESULTS The mean eGFRcr was higher than eGFRcys in both cohorts; absolute difference 22 mL/min/1.73 m2 (95% CI 21 to 23) in Nicaragua and 13 mL/min/1.73 m2 (95% CI 11 to 15) in El Salvador. Correlations between eGFRcr and eGFRcys were high, with r=0.69, 0.77 and 0.67 in Nicaragua at pre-harvest, end-harvest and cross-harvest, and r=0.89, 0.89 and 0.49 in El Salvador. CONCLUSIONS Creatinine increases among heat-stressed workers reflect reduced glomerular filtration as estimated using eGFRcys, a marker independent of muscle mass and metabolism. The discrepancy between eGFRcr and eGFRcys may indicate reduced glomerular filtration of larger molecules and/or systemic bias in CKD-EPI performance in this population.
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Affiliation(s)
- Axel Andersson
- School of Public Health and Community Medicine, University of Gothenburg Sahlgrenska Academy, Gothenburg, Sweden .,La Isla Network, Washington, District of Columbia, USA
| | - Erik Hansson
- School of Public Health and Community Medicine, University of Gothenburg Sahlgrenska Academy, Gothenburg, Sweden.,La Isla Network, Washington, District of Columbia, USA
| | - Ulf Ekström
- La Isla Network, Washington, District of Columbia, USA.,Department of Laboratory Medicine, Lund University, Lund, Sweden
| | - Anders Grubb
- Department of Laboratory Medicine, Lund University, Lund, Sweden
| | | | - Kristina Jakobsson
- School of Public Health and Community Medicine, University of Gothenburg Sahlgrenska Academy, Gothenburg, Sweden.,Occupational and Environmental Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Yiyi Xu
- School of Public Health and Community Medicine, University of Gothenburg Sahlgrenska Academy, Gothenburg, Sweden
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19
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Valiño-Rivas L, Cuarental L, Ceballos MI, Pintor-Chocano A, Perez-Gomez MV, Sanz AB, Ortiz A, Sanchez-Niño MD. Growth differentiation factor-15 preserves Klotho expression in acute kidney injury and kidney fibrosis. Kidney Int 2022; 101:1200-1215. [PMID: 35337892 DOI: 10.1016/j.kint.2022.02.028] [Citation(s) in RCA: 43] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Revised: 02/07/2022] [Accepted: 02/16/2022] [Indexed: 02/07/2023]
Abstract
Growth differentiation factor-15 (GDF15) is a member of the GDF subfamily with potential kidney protective functions. Here, we explored the impact of GDF15 on the expression of the kidney protective factor Klotho in models of acute kidney injury and kidney fibrosis in mice. GDF15 was the most upregulated GDF family gene in experimental toxic acute kidney injury and in kidney fibrosis transcriptomics. GDF15 function was explored in toxic acute kidney injury in genetically modified mice and following treatment with GDF15. Gdf15-deficient mice developed more severe toxic acute kidney injury (folic acid or cisplatin) while GDF15 overexpression or GDF15 administration were protective. Kidney expression of Klotho was more severely depressed in Gdf15-deficient mice and was preserved by GDF15 overexpression or GDF15 treatment. Moreover, increased plasma calcitriol levels inversely correlated with kidney Klotho across models with diverse levels of GDF15 availability. Kidney fibrosis induced by unilateral ureteral obstruction was more severe in Gdf15-deficient mice while GDF15 overexpression decreased kidney injury and preserved Klotho expression. GDF15 increased Klotho expression in vivo in healthy mice, in cultured tubular cells, and prevented Klotho downregulation by inflammatory factors in tubular cells by preventing transcription factor NF-ĸB activation. Thus, spontaneous increased kidney expression of endogenous GDF15 is not enough to prevent kidney injury, but further increments in GDF15 are kidney protecting and preserve expression of the kidney protective factor Klotho within the kidney in acute and chronic settings.
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Affiliation(s)
- Lara Valiño-Rivas
- Department of Nephrology and Hypertension. IIS-Fundacion Jimenez Diaz, School of Medicine, Universidad Autonoma de Madrid and REDINREN and FRIAT, Madrid, Spain
| | - Leticia Cuarental
- Department of Nephrology and Hypertension. IIS-Fundacion Jimenez Diaz, School of Medicine, Universidad Autonoma de Madrid and REDINREN and FRIAT, Madrid, Spain
| | - Maria I Ceballos
- Department of Nephrology and Hypertension. IIS-Fundacion Jimenez Diaz, School of Medicine, Universidad Autonoma de Madrid and REDINREN and FRIAT, Madrid, Spain
| | - Arancha Pintor-Chocano
- Department of Nephrology and Hypertension. IIS-Fundacion Jimenez Diaz, School of Medicine, Universidad Autonoma de Madrid and REDINREN and FRIAT, Madrid, Spain
| | - Maria Vanessa Perez-Gomez
- Department of Nephrology and Hypertension. IIS-Fundacion Jimenez Diaz, School of Medicine, Universidad Autonoma de Madrid and REDINREN and FRIAT, Madrid, Spain
| | - Ana B Sanz
- Department of Nephrology and Hypertension. IIS-Fundacion Jimenez Diaz, School of Medicine, Universidad Autonoma de Madrid and REDINREN and FRIAT, Madrid, Spain
| | - Alberto Ortiz
- Department of Nephrology and Hypertension. IIS-Fundacion Jimenez Diaz, School of Medicine, Universidad Autonoma de Madrid and REDINREN and FRIAT, Madrid, Spain
| | - Maria Dolores Sanchez-Niño
- Department of Nephrology and Hypertension. IIS-Fundacion Jimenez Diaz, School of Medicine, Universidad Autonoma de Madrid and REDINREN and FRIAT, Madrid, Spain; Department of Pharmacology, Universidad Autonoma de Madrid, Madrid, Spain.
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20
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Poudyal A, Karki KB, Shrestha N, Aryal KK, Mahato NK, Bista B, Ghimire L, Kc D, Gyanwali P, Jha AK, Garcia-Larsen V, Kuch U, Groneberg DA, Sharma SK, Dhimal M. Prevalence and risk factors associated with chronic kidney disease in Nepal: evidence from a nationally representative population-based cross-sectional study. BMJ Open 2022; 12:e057509. [PMID: 35314475 PMCID: PMC8938697 DOI: 10.1136/bmjopen-2021-057509] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Accepted: 02/15/2022] [Indexed: 11/04/2022] Open
Abstract
OBJECTIVE This study aimed to determine population-based prevalence of chronic kidney disease (CKD) and its associated factors in Nepal. STUDY DESIGN The study was a nationwide population-based cross-sectional study. SETTING AND PARTICIPANTS Cross-sectional survey conducted in a nationally representative sample of 12 109 Nepalese adult from 2016 to 2018 on selected chronic non-communicable diseases was examined. Multistage cluster sampling with a mix of probability proportionate to size and systematic random sampling was used for the selection of individuals aged 20 years and above. PRIMARY AND SECONDARY OUTCOME MEASURES Primary outcome in this study was population-based prevalence of CKD in Nepal. A participant was considered to have CKD if the urine albumin-to-creatinine ratio was greater than or equal to 30 mg/g and/or estimated glomerular filtration rate is less than 60 mL/min/1.73 m2 at baseline and in follow-up using modification of diet in renal disease study equations. The secondary outcome measure was factors associated with CKD in Nepal. The covariate adjusted association of risk factors and CKD was calculated using multivariable binary logistic regression. RESULTS The overall prevalence of CKD in Nepal was 6.0% (95% CI 5.5 to 6.6). Factors independently associated with CKD included older age (adjusted OR (AOR) 2.6, 95% CI 1.9 to 3.6), Dalit caste (AOR 1.6, 95% CI 1.1 to 2.3), hypertension (AOR 2.4, 95% CI 2.0 to 3.0), diabetes mellitus (AOR 3.2, 95% CI 2.5 to 4.1), raised total cholesterol (AOR 1.3, 95% CI 1.0 to 1.6) and increased waist-to-hip ratio (AOR 1.6, 95% CI 1.2 to 2.3). CONCLUSION This nationally representative study shows that the prevalence of CKD in the adult population of Nepal is substantial, and it is independently associated with several cardiometabolic traits. These findings warrant longitudinal studies to identify the causes of CKD in Nepal and effective strategies to prevent it.
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Affiliation(s)
- Anil Poudyal
- Research section, Nepal Health Research Council, Ramshah path, Kathmandu, Nepal
| | - Khem Bahadur Karki
- Institute of Occupational, Social and Environmental Medicine, Goethe University Frankfurt, Frankfurt am Main, Hessen, Germany
- Department of Community Medicine, Maharajgunj Medical Campus, Kathmandu, Nepal
| | - Namuna Shrestha
- Public Health Promotion and Development Organization, Kathmandu, Nepal
| | | | - Namra Kumar Mahato
- Research section, Nepal Health Research Council, Ramshah path, Kathmandu, Nepal
| | - Bihungum Bista
- Research section, Nepal Health Research Council, Ramshah path, Kathmandu, Nepal
| | - Laxmi Ghimire
- Sanjeevani College of Medical Sciences, Rupandehi, Nepal
| | - Dirghayu Kc
- Public Health Promotion and Development Organization, Kathmandu, Nepal
| | - Pradip Gyanwali
- Research section, Nepal Health Research Council, Ramshah path, Kathmandu, Nepal
| | - Anjani Kumar Jha
- Research section, Nepal Health Research Council, Ramshah path, Kathmandu, Nepal
| | - Vanessa Garcia-Larsen
- Department of International Health, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
| | - Ulrich Kuch
- Institute of Occupational, Social and Environmental Medicine, Goethe University Frankfurt, Frankfurt am Main, Hessen, Germany
| | - David A Groneberg
- Institute of Occupational, Social and Environmental Medicine, Goethe University Frankfurt, Frankfurt am Main, Hessen, Germany
| | - Sanjib Kumar Sharma
- Department of Internal Medicine, BP Koirala Institute of Health Sciences, Dharan, Nepal
| | - Meghnath Dhimal
- Research section, Nepal Health Research Council, Ramshah path, Kathmandu, Nepal
- Institute of Occupational, Social and Environmental Medicine, Goethe University Frankfurt, Frankfurt am Main, Hessen, Germany
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21
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Metformin Protects Against Cardiac and Renal Damage in Diabetic Cardiac Arrest Patients. Resuscitation 2022; 174:42-46. [PMID: 35331801 PMCID: PMC9050929 DOI: 10.1016/j.resuscitation.2022.03.017] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 03/11/2022] [Accepted: 03/16/2022] [Indexed: 11/22/2022]
Abstract
INTRODUCTION Metformin is a first-line diabetic therapy that improves survival in a wide number of ischemic pathologies. We tested the association of metformin with markers of cardiac and renal injury in diabetic post-arrest patients. METHODS We performed a retrospective analysis of clinical outcomes in diabetic cardiac arrest patients with and without metformin therapy at a single academic medical center. We used generalized linear models to test the independent association of metformin, insulin, and other hypoglycemic agents with peak 24-hour serum creatinine and peak 24-hour serum troponin. RESULTS Metformin prescription at the time of SCA was independently associated with lower 24-hour peak serum troponin and lower 24-hour peak serum creatinine when compared to non-metformin patients. CONCLUSION Metformin pretreatment may offer cardiac and renal protection for diabetic patients during sudden cardiac arrest.
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22
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Mutatiri C, Ratsch A, McGrail MR, Venuthurupalli S, Kondalsamy Chennakesavan S. Referral patterns, disease progression and impact of the kidney failure risk equation (KFRE) in a Queensland Chronic Kidney Disease Registry (CKD.QLD) cohort: a study protocol. BMJ Open 2022; 12:e052790. [PMID: 35193907 PMCID: PMC8867303 DOI: 10.1136/bmjopen-2021-052790] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Accepted: 01/24/2022] [Indexed: 11/07/2022] Open
Abstract
INTRODUCTION Chronic kidney disease (CKD) is a rapidly increasing and global phenomenon which carries high morbidity and mortality. Although timely referral from primary care to secondary care confers favourable outcomes, it is not possible for every patient with CKD to be managed at secondary care. With 1 in 10 Australians currently living with markers of CKD against a workforce of about 600 nephrology specialists, a risk stratification strategy is required that will reliably identify individuals whose kidney disease is likely to progress. METHODS AND ANALYSIS This study will undertake a retrospective secondary analysis of the Chronic Kidney Disease Queensland Registry (CKD.QLD) data of consented adults to examine the referral patterns to specialist nephrology services from primary care providers and map the patient trajectory and outcomes to inform the optimal referral timing for disease mitigation. Patient data over a 5-year period will be examined to determine the impact of the kidney failure risk equation-based risk stratification on the referral patterns, disease progression and patient outcomes. The results will inform considerations of a risk stratification strategy that will ensure adequate predialysis management and add to the discussion of the time interval between referral and initiation of kidney replacement therapy or development of cardiovascular events. ETHICS AND DISSEMINATION This protocol was approved by the Ethics Committee of the Royal Brisbane and Women's Hospital in January 2021 (LNR/2020/QRBW/69707 14/01/2021). The HREC waived the requirement for patient consent as all patients had consented for the use of their data for the purpose of research on recruitment into CKD.QLD Registry. The results will be presented as a component of a PhD study with The University of Queensland. It is anticipated that the results will be presented at health-related conferences (local, national and possibly international) and via publication in peer-reviewed academic journals.
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Affiliation(s)
- Clyson Mutatiri
- Renal Medicine, Wide Bay Hospital and Health Service, Bundaberg, Queensland, Australia
- Rural Clinical School, Faculty of Medicine, The University of Queensland, Bundaberg, Queensland, Australia
| | - Angela Ratsch
- Research Services, Wide Bay Hospital and Health Service, Hervey Bay, Queensland, Australia
- Rural Clinical School, Faculty of Medicine, The University of Queensland, Hervey Bay, Queensland, Australia
| | - Matthew R McGrail
- Rural Clinical School, Faculty of Medicine, The University of Queensland, Rockhampton, Queensland, Australia
| | - Sree Venuthurupalli
- Kidney Service, Department of Medicine, West Moreton Hospital and Health Service, Ipswich, Queensland, Australia
- Rural Clinical School, Faculty of Medicine, The University of Queensland, Toowoomba, Queensland, Australia
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23
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Protective effect of aqueous leaf extracts of Chromolaena odorata and Tridax procumbens on doxorubicin-induced hepatotoxicity in Wistar rats. Porto Biomed J 2021; 6:e143. [PMID: 34881354 PMCID: PMC8647896 DOI: 10.1097/j.pbj.0000000000000143] [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: 01/11/2021] [Revised: 02/20/2021] [Accepted: 03/14/2021] [Indexed: 11/30/2022] Open
Abstract
Background: The liver is one of the organs affected by doxorubicin toxicity. Therefore, in this study, the potential protective role of aqueous leaf extracts of Chromolaena odorata and Tridax procumbens against doxorubicin-induced hepatotoxicity was investigated. Methods: In order to achieve this, their impact on hepatic biomarkers of oxidative stress, lipid and electrolytes’ profile, and plasma biomarkers of liver functions/integrity were monitored in doxorubicin treated rats. The animals were treated with either metformin (250 mg/kg body weight orally for 14 days) or the extracts (50, 75, and 100 mg/kg orally for 14 days) and/or doxorubicin (15 mg/kg, intraperitoneal, 48 h before sacrifice). Results: The hepatic malondialdehyde, cholesterol, calcium, and sodium concentrations, and plasma activities of alanine and aspartate transaminases and alkaline phosphatase, as well as plasma albumin to globulin ratio of test control were significantly (P < .05) higher than those of all the other groups. However, the plasma albumin, total protein, globulin, and total bilirubin concentrations; hepatic concentrations of ascorbic acid, chloride, magnesium, and potassium; and hepatic activities of catalase, glutathione peroxidase, and superoxide dismutase of test control were significantly (P < .05) lower than those of all the other groups. Conclusions: Pretreatment with the extracts and metformin prevented to varying degrees, doxorubicin-induced hepatic damage, as indicated by the attenuation of doxorubicin-induced adverse alterations in hepatic biomarkers of oxidative stress, lipid and electrolyte profiles, and plasma biomarkers of hepatic function/integrity, and keeping them at near-normal values.
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24
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Noyes J, Roberts G, Williams G, Chess J, Mc Laughlin L. Understanding the low take-up of home-based dialysis through a shared decision-making lens: a qualitative study. BMJ Open 2021; 11:e053937. [PMID: 34845074 PMCID: PMC8634024 DOI: 10.1136/bmjopen-2021-053937] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2021] [Accepted: 10/21/2021] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVES To explore how people with chronic kidney disease who are pre-dialysis, family members and healthcare professionals together navigate common shared decision-making processes and to assess how this impacts future treatment choice. DESIGN Coproductive qualitative study, underpinned by the Making Good Decisions in Collaboration shared decision-model. Semistructured interviews with a purposive sample from February 2019 - January 2020. Interview data were analysed using framework analysis. Coproduction of logic models/roadmaps and recommendations. SETTING Five Welsh kidney services. PARTICIPANTS 95 participants (37 patients, 19 family members and 39 professionals); 44 people supported coproduction (18 patients, 8 family members and 18 professionals). FINDINGS Shared decision-making was too generic and clinically focused and had little impact on people getting onto home dialysis. Preferences of where, when and how to implement shared decision-making varied widely. Apathy experienced by patients, caused by lack of symptoms, denial, social circumstances and health systems issues made future treatment discussions difficult. Families had unmet and unrecognised needs, which significantly influenced patient decisions. Protocols containing treatment hierarchies and standards were understood by professionals but not translated for patients and families. Variation in dialysis treatment was discussed to match individual lifestyles. Patients and professionals were, however, defaulting to the perceived simplest option. It was easy for patients to opt for hospital-based treatments by listing important but easily modifiable factors. CONCLUSIONS Shared decision-making processes need to be individually tailored with more attention on patients who could choose a home therapy but select a different option. There are critical points in the decision-making process where changes could benefit patients. Patients need to be better educated and their preconceived ideas and misconceptions gently challenged. Healthcare professionals need to update their knowledge in order to provide the best advice and guidance. There needs to be more awareness of the costs and benefits of the various treatment options when making decisions.
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Affiliation(s)
- Jane Noyes
- School of Medical and Health Sciences, Bangor University, Bangor, UK
| | - Gareth Roberts
- Department of Nephrology, Cardiff and Vale University Health Board, Cardiff, UK
| | | | - James Chess
- Renal Unit, Swansea Bay University Health Board, Port Talbot, UK
| | - Leah Mc Laughlin
- School of Medical and Health Sciences, Bangor University, Bangor, UK
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25
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Xue X, Lu CL, Jin XY, Liu XH, Yang M, Wang XQ, Cheng H, Yuan J, Liu Q, Zheng RX, Robinson N, Liu JP. Relationship between serum uric acid, all-cause mortality and cardiovascular mortality in peritoneal dialysis patients: systematic review and meta-analysis of cohort studies. BMJ Open 2021; 11:e052274. [PMID: 34663666 PMCID: PMC8524295 DOI: 10.1136/bmjopen-2021-052274] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
OBJECTIVES To analyse the relationship between serum uric acid (SUA), all-cause and cardiovascular (CV) mortality in peritoneal dialysis (PD) patients to inform clinical practice and future research. DESIGN A systematic review of observational studies. DATA SOURCES PubMed, Embase, Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), SinoMed, Chinese Science and Technology Journal Database (VIP) and Wan Fang databases were searched from their inception to January 2021 for cohort and case-control studies reporting SUA and mortality in patients with PD. METHODS The Newcastle-Ottawa Quality Assessment Scale was used to appraise quality of cohort and case-control studies. Effect estimates were presented as HRs with 95% CIs in a meta-analysis using STATA V.16.0. Data not suitable for pooling were synthesised qualitatively. RESULTS Fourteen cohort studies with 24 022 patients were included. No case-control studies were identified. For prospective cohort studies, pooled results for the highest SUA category were significantly greater than the lowest for all-cause (one study; 1278participants; HR 1.79; 95% CI 1.17 to 2.75) and CV mortality (one study; 1278 participants; HR 2.63; 1.62-4.27). An increase of 1 mg/dL in SUA level was associated with a 16% increased risk of all-cause mortality (one study; 1278 participants; HR 1.16; 1.03-1.32) and 34% increased CV mortality risk (one study; 1278 participants; HR 1.34; 1.16-1.55). For retrospective cohort studies, the highest SUA category did not demonstrate an elevated all-cause (five studies; 4570 participants; HR 1.09; 0.70-1.70) or CV mortality (three studies; 3748 participants; HR 1.00; 0.44-2.31) compared with the lowest SUA category. Additionally, there was no increase in all-cause (eight studies; 11 541 participants; HR 0.94; 0.88-1.02) or CV mortality (three studies; 7427 participants; HR 0.90; 0.76-1.06) for every 1 mg/dL increase in SUA level. CONCLUSIONS Results of prospective and retrospective cohort studies were inconsistent. Consequently, prospective, multicentre, long-term follow-up studies are required to confirm the relationship between SUA and mortality in patients with PD.
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Affiliation(s)
- Xue Xue
- First Clinical College and Affiliated Hospital, Hubei University of Traditional Chinese Medicine, Wuhan, China
- Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Chun-Li Lu
- Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Xin-Yan Jin
- Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Xue-Han Liu
- Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Min Yang
- Basic Medical School, Hubei University of Traditional Chinese Medicine, Wuhan, China
| | - Xiao-Qin Wang
- Department of Nephrology, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China
| | - Hong Cheng
- Department of Nephrology, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China
| | - Jun Yuan
- Department of Nephrology, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China
| | - Qiang Liu
- Department of Cardiology, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China
| | - Ruo-Xiang Zheng
- Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Nicola Robinson
- Institute of Health and Social Care, London South Bank University, London, UK
| | - Jian-Ping Liu
- Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
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26
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Chekol Tassew W, Birhan N, Zewdu Y. Incidence and Predictors of Acute Kidney Injury Among Newly Diagnosed Type 2 Diabetes Patients at Chronic Follow-Up Clinic of University of Gondar Comprehensive Specialized Hospital: A Retrospective Follow-Up Study. Res Rep Urol 2021; 13:613-622. [PMID: 34466407 PMCID: PMC8403085 DOI: 10.2147/rru.s306467] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Accepted: 08/11/2021] [Indexed: 11/23/2022] Open
Abstract
Background Acute kidney injury is a common disorder worldwide, occurring in more than 13 million per year, 85% of whom live in developing countries. The high incidence of acute kidney injury among type 2 diabetic patients is a major cause of morbidity and mortality. There is limited data that address the incidence and predictors of acute kidney injury to apply evidence-based interventions in developing countries including Ethiopia specifically in the study area. Methods Institution-based retrospective follow-up study was conducted among 420 adults with newly diagnosed type 2 diabetes patients from January 1, 2014, to December 31, 2019. Log rank test and Kaplan–Meier curve were used to compare different categories of survival probability. In a multivariable analysis, variable having a p-value <0.05 in the Cox, proportional hazard model was considered as independent predictors. Results Overall, 19.76% (95% CI; 16.2–23.8) of the study population developed acute kidney injury, with a median follow-up period of 30.75 months. Congestive heart failure [adjusted hazard ratio (AHR): 2.89 (95% CI; 1.62, 5.13)], chronic kidney disease [AHR: 2.92 (95% CI; 1.56, 5.48)], hypertension [AHR: 2.87 (95% CI; 1.20, 6.90)], and diabetic nephropathy [AHR: 2.04 (95% CI; 1.13, 3.68)] were found to be predictors of acute kidney injury. Conclusion The incidence of acute kidney injury among type 2 diabetes patients was high in the study area. In patients with hypertension congestive heart failure, chronic kidney disease, and diabetic nephropathy efforts should be made to diagnose AKI early and treat it – in addition to better control accordingly among type 2 diabetes mellitus patients.
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Affiliation(s)
- Worku Chekol Tassew
- School of Nursing, College of Medicine and Health Sciences, Department of Medical Nursing, University of Gondar, Gondar, Ethiopia
| | - Nigussie Birhan
- School of Nursing, College of Medicine and Health Sciences, Departments of Community Health Nursing, University of Gondar, Gondar, Ethiopia
| | - Yemataw Zewdu
- Department of Emergency and Critical Care Nursing, School of Nursing, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
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Orloff J, Min JY, Mushlin A, Flory J. Safety and effectiveness of metformin in patients with reduced renal function: A systematic review. Diabetes Obes Metab 2021; 23:2035-2047. [PMID: 34009711 DOI: 10.1111/dom.14440] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 05/12/2021] [Accepted: 05/12/2021] [Indexed: 12/15/2022]
Abstract
AIM To examine clinical and safety outcomes associated with metformin use in patients with impaired renal function. MATERIALS AND METHODS We searched PubMed and Embase databases from inception to August 2020, supplementing our search with a review of investigator files and reference lists of included studies. Any study reporting original data on metformin and patient-centred outcomes in patients with impaired renal function, defined as an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73m2 , was included. Post hoc meta-analysis was performed for the outcomes of mortality, cardiovascular events and acidosis. RESULTS Nine small prospective studies enrolling patients with significantly impaired renal function identified only one case of clinically apparent lactic acidosis. Among 13 larger retrospective studies, seven examined the risk of mortality across patient subgroups; meta-analysis showed reductions in overall mortality at an eGFR of 45 mL/min/1.73m2 or higher but not at an eGFR of less than 45 mL/min/1.73m2 . Eight retrospective studies evaluated acidosis as an outcome; meta-analysis showed no increase in risk of acidosis except at an eGFR of less than 30 mL/min/1.73m2 , in which group the HR was 1.97 (95% CI 1.03-3.77). CONCLUSIONS The literature shows metformin to be associated with reduced mortality and no increased risk of acidosis at an eGFR of 45 mL/min/1.73m2 or higher. Metformin appears to be associated with fewer benefits and possible increases in the risk of acidosis at an eGFR of less than 30 mL/min/1.73m2 . Consistent with US Food and Drug Administration guidelines, metformin should not be used at an eGFR less than 30 mL/min/1.73m2 , and further research on its risk-benefit profile at eGFR values approaching 30 mL/min/1.73m2 is warranted.
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Affiliation(s)
- Jeremy Orloff
- Weill Cornell Medical College, New York, New York, USA
| | - Jea Young Min
- Weill Cornell Medical College, New York, New York, USA
| | - Alvin Mushlin
- Weill Cornell Medical College, New York, New York, USA
| | - James Flory
- Memorial Sloan Kettering Cancer Center, New York, New York, USA
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28
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Induri SNR, Kansara P, Thomas SC, Xu F, Saxena D, Li X. The Gut Microbiome, Metformin, and Aging. Annu Rev Pharmacol Toxicol 2021; 62:85-108. [PMID: 34449247 DOI: 10.1146/annurev-pharmtox-051920-093829] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Metformin has been extensively used for the treatment of type 2 diabetes, and it may also promote healthy aging. Despite its widespread use and versatility, metformin's mechanisms of action remain elusive. The gut typically harbors thousands of bacterial species, and as the concentration of metformin is much higher in the gut as compared to plasma, it is plausible that microbiome-drug-host interactions may influence the functions of metformin. Detrimental perturbations in the aging gut microbiome lead to the activation of the innate immune response concomitant with chronic low-grade inflammation. With the effectiveness of metformin in diabetes and antiaging varying among individuals, there is reason to believe that the gut microbiome plays a role in the efficacy of metformin. Metformin has been implicated in the promotion and maintenance of a healthy gut microbiome and reduces many age-related degenerative pathologies. Mechanistic understanding of metformin in the promotion of a healthy gut microbiome and aging will require a systems-level approach. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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Affiliation(s)
- Sri Nitya Reddy Induri
- Department of Molecular Pathobiology, New York University College of Dentistry, New York, NY 10010, USA;
| | - Payalben Kansara
- Department of Molecular Pathobiology, New York University College of Dentistry, New York, NY 10010, USA;
| | - Scott C Thomas
- Department of Molecular Pathobiology, New York University College of Dentistry, New York, NY 10010, USA;
| | - Fangxi Xu
- Department of Molecular Pathobiology, New York University College of Dentistry, New York, NY 10010, USA;
| | - Deepak Saxena
- Department of Molecular Pathobiology, New York University College of Dentistry, New York, NY 10010, USA; .,Department of Surgery, New York University School of Medicine, New York, NY 10016, USA
| | - Xin Li
- Department of Molecular Pathobiology, New York University College of Dentistry, New York, NY 10010, USA;
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29
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De Broe ME, Jouret F. Does metformin do more benefit or harm in chronic kidney disease patients? Kidney Int 2021; 98:1098-1101. [PMID: 33126974 DOI: 10.1016/j.kint.2020.04.059] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Revised: 03/30/2020] [Accepted: 04/02/2020] [Indexed: 12/13/2022]
Affiliation(s)
- Marc E De Broe
- Laboratory Physiopathology, University of Antwerp, Liège, Belgium.
| | - François Jouret
- Research Department of Pathophysiology, Department Nephrology, University Hospital of Liège, Antwerpen, Belgium.
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30
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García-Carro C, Vergara A, Bermejo S, Azancot MA, Sánchez-Fructuoso AI, Sánchez de la Nieta MD, Agraz I, Soler MJ. How to Assess Diabetic Kidney Disease Progression? From Albuminuria to GFR. J Clin Med 2021; 10:jcm10112505. [PMID: 34198818 PMCID: PMC8201333 DOI: 10.3390/jcm10112505] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Revised: 06/02/2021] [Accepted: 06/03/2021] [Indexed: 12/12/2022] Open
Abstract
Diabetic kidney disease (DKD) is one of the most relevant complications of type 2 diabetes and dramatically increases the cardiovascular risk in these patients. Currently, DKD is severely infra-diagnosed, or its diagnosis is usually made at advanced stages of the disease. During the last decade, new drugs have demonstrated a beneficial effect in terms of cardiovascular and renal protection in type 2 diabetes, supporting the crucial role of an early DKD diagnosis to permit the use of new available therapeutic strategies. Moreover, cardiovascular and renal outcome trials, developed to study these new drugs, are based on diverse cardiovascular and renal simple and composite endpoints, which makes difficult their interpretation and the comparison between them. In this article, DKD diagnosis is reviewed, focusing on albuminuria and the recommendations for glomerular filtration rate measurement. Furthermore, cardiovascular and renal endpoints used in classical and recent cardiovascular outcome trials are assessed in a pragmatic way.
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Affiliation(s)
- Clara García-Carro
- Nephrology Department, San Carlos Clinical University Hospital, 28040 Madrid, Spain; (C.G.-C.); (A.I.S.-F.); (M.D.S.d.l.N.)
| | - Ander Vergara
- Nephrology Research Group, Nephrology Department, Vall d’Hebrón Research Institute (VHIR), Vall d’Hebron Barcelona Hospital Campus, Vall d’Hebrón Hospital Universitari, 08035 Barcelona, Spain; (A.V.); (S.B.); (M.A.A.)
| | - Sheila Bermejo
- Nephrology Research Group, Nephrology Department, Vall d’Hebrón Research Institute (VHIR), Vall d’Hebron Barcelona Hospital Campus, Vall d’Hebrón Hospital Universitari, 08035 Barcelona, Spain; (A.V.); (S.B.); (M.A.A.)
| | - María A. Azancot
- Nephrology Research Group, Nephrology Department, Vall d’Hebrón Research Institute (VHIR), Vall d’Hebron Barcelona Hospital Campus, Vall d’Hebrón Hospital Universitari, 08035 Barcelona, Spain; (A.V.); (S.B.); (M.A.A.)
| | - Ana I. Sánchez-Fructuoso
- Nephrology Department, San Carlos Clinical University Hospital, 28040 Madrid, Spain; (C.G.-C.); (A.I.S.-F.); (M.D.S.d.l.N.)
| | - M. Dolores Sánchez de la Nieta
- Nephrology Department, San Carlos Clinical University Hospital, 28040 Madrid, Spain; (C.G.-C.); (A.I.S.-F.); (M.D.S.d.l.N.)
| | - Irene Agraz
- Nephrology Research Group, Nephrology Department, Vall d’Hebrón Research Institute (VHIR), Vall d’Hebron Barcelona Hospital Campus, Vall d’Hebrón Hospital Universitari, 08035 Barcelona, Spain; (A.V.); (S.B.); (M.A.A.)
- Correspondence: (I.A.); (M.J.S.)
| | - María José Soler
- Nephrology Research Group, Nephrology Department, Vall d’Hebrón Research Institute (VHIR), Vall d’Hebron Barcelona Hospital Campus, Vall d’Hebrón Hospital Universitari, 08035 Barcelona, Spain; (A.V.); (S.B.); (M.A.A.)
- Correspondence: (I.A.); (M.J.S.)
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Stanescu AMA, Simionescu AA, Florea M, Diaconu CC. Is Metformin a Possible Beneficial Treatment for Psoriasis? A Scoping Review. J Pers Med 2021; 11:251. [PMID: 33808460 PMCID: PMC8065978 DOI: 10.3390/jpm11040251] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 03/24/2021] [Accepted: 03/26/2021] [Indexed: 02/06/2023] Open
Abstract
Psoriasis is a chronic inflammatory condition with genetic, immunological, and metabolic etiology. The link between psoriasis and diabetes mellitus has been shown in genetic predisposition, environmental influences, inflammatory pathways, and insulin resistance, resulting in end-organ damage in both conditions. Because comorbidities often accompany psoriasis, the therapeutic management of the disease must also take into consideration the comorbidities. Given that metformin's therapeutic role in psoriasis is not yet fully elucidated, we raised the question of whether metformin is a viable alternative for the treatment of psoriasis. We conducted this scoping review by searching for evidence in PubMed, Cochrane, and Scopus databases, and we used an extension for scoping reviews (PRISMA-ScR). Current evidence suggests that metformin is safe to use in psoriasis. Studies have shown an excellent therapeutic response to metformin in patients with psoriasis and comorbidities such as diabetes, metabolic syndrome, and obesity. There is no clear evidence supporting metformin monotherapy in patients with psoriasis without comorbidities. There is a need to further evaluate metformin in larger clinical trials, as a therapy in psoriasis.
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Affiliation(s)
| | - Anca Angela Simionescu
- Department of Obstetrics and Gynecology, Filantropia Clinical Hospital, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Mira Florea
- Community Medicine Department, Iuliu Hatieganu University of Medicine and Pharmacy, 400000 Cluj-Napoca, Romania
| | - Camelia Cristina Diaconu
- Department of Internal Medicine, Clinical Emergency Hospital of Bucharest, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania;
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Drzewoski J, Hanefeld M. The Current and Potential Therapeutic Use of Metformin-The Good Old Drug. Pharmaceuticals (Basel) 2021; 14:122. [PMID: 33562458 PMCID: PMC7915435 DOI: 10.3390/ph14020122] [Citation(s) in RCA: 67] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 02/02/2021] [Accepted: 02/02/2021] [Indexed: 02/07/2023] Open
Abstract
Metformin, one of the oldest oral antidiabetic agents and still recommended by almost all current guidelines as the first-line treatment for type 2 diabetes mellitus (T2DM), has become the medication with steadily increasing potential therapeutic indications. A broad spectrum of experimental and clinical studies showed that metformin has a pleiotropic activity and favorable effect in different pathological conditions, including prediabetes, type 1 diabetes mellitus (T1DM) and gestational diabetes mellitus (GDM). Moreover, there are numerous studies, meta-analyses and population studies indicating that metformin is safe and well tolerated and may be associated with cardioprotective and nephroprotective effect. Recently, it has also been reported in some studies, but not all, that metformin, besides improvement of glucose homeostasis, may possibly reduce the risk of cancer development, inhibit the incidence of neurodegenerative disease and prolong the lifespan. This paper presents some arguments supporting the initiation of metformin in patients with newly diagnosed T2DM, especially those without cardiovascular risk factors or without established cardiovascular disease or advanced kidney insufficiency at the time of new guidelines favoring new drugs with pleotropic effects complimentary to glucose control. Moreover, it focuses on the potential beneficial effects of metformin in patients with T2DM and coexisting chronic diseases.
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Affiliation(s)
- Józef Drzewoski
- Central Teaching Hospital of Medical University of Lodz, 92-213 Lodz, Poland
| | - Markolf Hanefeld
- Medical Clinic III, Department of Medicine Technical University Dresden, 01307 Dresden, Germany;
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33
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Bai B, Chen H. Metformin: A Novel Weapon Against Inflammation. Front Pharmacol 2021; 12:622262. [PMID: 33584319 PMCID: PMC7880161 DOI: 10.3389/fphar.2021.622262] [Citation(s) in RCA: 83] [Impact Index Per Article: 20.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Accepted: 01/04/2021] [Indexed: 12/11/2022] Open
Abstract
It has become widely accepted that inflammation is a driving force behind a variety of chronic diseases, such as cardiovascular disease, diabetes, kidney disease, cancer, neurodegenerative disorders, etc. However, the existing nonsteroidal anti-inflammatory drugs show a limited utility in clinical patients. Therefore, the novel agents with different inflammation-inhibitory mechanisms are worth pursuing. Metformin, a synthetic derivative of guanidine, has a history of more than 50 years of clinical experience in treating patients with type 2 diabetes. Intense research efforts have been dedicated to proving metformin’s inflammation-inhibitory effects in cells, animal models, patient records, and randomized clinical trials. The emerging evidence also indicates its therapeutic potential in clinical domains other than type 2 diabetes. Herein, this article appraises current pre-clinical and clinical findings, emphasizing metformin’s anti-inflammatory properties under individual pathophysiological scenarios. In summary, the anti-inflammatory effects of metformin are evident in pre-clinical models. By comparison, there are still clinical perplexities to be addressed in repurposing metformin to inflammation-driven chronic diseases. Future randomized controlled trials, incorporating better stratification/targeting, would establish metformin’s utility in this clinical setting.
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Affiliation(s)
- Bo Bai
- Department of Cardiology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, China
| | - Haibo Chen
- Department of Cardiology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, China
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34
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Shpakov AO. Improvement Effect of Metformin on Female and Male Reproduction in Endocrine Pathologies and Its Mechanisms. Pharmaceuticals (Basel) 2021; 14:ph14010042. [PMID: 33429918 PMCID: PMC7826885 DOI: 10.3390/ph14010042] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Revised: 01/02/2021] [Accepted: 01/06/2021] [Indexed: 02/07/2023] Open
Abstract
Metformin (MF), a first-line drug to treat type 2 diabetes mellitus (T2DM), alone and in combination with other drugs, restores the ovarian function in women with polycystic ovary syndrome (PCOS) and improves fetal development, pregnancy outcomes and offspring health in gestational diabetes mellitus (GDM) and T2DM. MF treatment is demonstrated to improve the efficiency of in vitro fertilization and is considered a supplementary drug in assisted reproductive technologies. MF administration shows positive effect on steroidogenesis and spermatogenesis in men with metabolic disorders, thus MF treatment indicates prospective use for improvement of male reproductive functions and fertility. MF lacks teratogenic effects and has positive health effect in newborns. The review is focused on use of MF therapy for restoration of female and male reproductive functions and improvement of pregnancy outcomes in metabolic and endocrine disorders. The mechanisms of MF action are discussed, including normalization of metabolic and hormonal status in PCOS, GDM, T2DM and metabolic syndrome and restoration of functional activity and hormonal regulation of the gonadal axis.
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Affiliation(s)
- Alexander O Shpakov
- I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of Russian Academy of Sciences, 194223 Saint Petersburg, Russia
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35
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Hapca S, Siddiqui MK, Kwan RS, Lim M, Matthew S, Doney AS, Pearson ER, Palmer CN, Bell S, on behalf of the BEAt-DKD Consortium. The Relationship between AKI and CKD in Patients with Type 2 Diabetes: An Observational Cohort Study. J Am Soc Nephrol 2021; 32:138-150. [PMID: 32948670 PMCID: PMC7894655 DOI: 10.1681/asn.2020030323] [Citation(s) in RCA: 70] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Accepted: 07/27/2020] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND There are few observational studies evaluating the risk of AKI in people with type 2 diabetes, and even fewer simultaneously investigating AKI and CKD in this population. This limits understanding of the interplay between AKI and CKD in people with type 2 diabetes compared with the nondiabetic population. METHODS In this retrospective, cohort study of participants with or without type 2 diabetes, we used electronic healthcare records to evaluate rates of AKI and various statistical methods to determine their relationship to CKD status and further renal function decline. RESULTS We followed the cohort of 16,700 participants (9417 with type 2 diabetes and 7283 controls without diabetes) for a median of 8.2 years. Those with diabetes were more likely than controls to develop AKI (48.6% versus 17.2%, respectively) and have preexisting CKD or CKD that developed during follow-up (46.3% versus 17.2%, respectively). In the absence of CKD, the AKI rate among people with diabetes was nearly five times that of controls (121.5 versus 24.6 per 1000 person-years). Among participants with CKD, AKI rate in people with diabetes was more than twice that of controls (384.8 versus 180.0 per 1000 person-years after CKD diagnostic date, and 109.3 versus 47.4 per 1000 person-years before CKD onset in those developing CKD after recruitment). Decline in eGFR slope before AKI episodes was steeper in people with diabetes versus controls. After AKI episodes, decline in eGFR slope became steeper in people without diabetes, but not among those with diabetes and preexisting CKD. CONCLUSIONS Patients with diabetes have significantly higher rates of AKI compared with patients without diabetes, and this remains true for individuals with preexisting CKD.
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Affiliation(s)
- Simona Hapca
- Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, United Kingdom,Division of Computing Science and Mathematics, University of Stirling, Stirling, United Kingdom
| | - Moneeza K. Siddiqui
- Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, United Kingdom
| | - Ryan S.Y. Kwan
- Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, United Kingdom
| | - Michelle Lim
- Renal Unit, Ninewells Hospital, Dundee, United Kingdom
| | - Shona Matthew
- Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, United Kingdom
| | - Alex S.F. Doney
- Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, United Kingdom
| | - Ewan R. Pearson
- Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, United Kingdom
| | - Colin N.A. Palmer
- Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, United Kingdom
| | - Samira Bell
- Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, United Kingdom,Renal Unit, Ninewells Hospital, Dundee, United Kingdom
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Mariano F, Biancone L. Metformin, chronic nephropathy and lactic acidosis: a multi-faceted issue for the nephrologist. J Nephrol 2020; 34:1127-1135. [PMID: 33373028 PMCID: PMC8357762 DOI: 10.1007/s40620-020-00941-8] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Accepted: 11/30/2020] [Indexed: 12/15/2022]
Abstract
Metformin is currently considered a first-line therapy in type 2 diabetic patients. After issuing warnings for decades about the risks of lactic acidosis in patients with chronic nephropathy, metformin is now being re-evaluated. The most recent evidence from the literature has demonstrated both a low, acceptable risk of lactic acidosis and a series of favorable effects, which go beyond its hypoglycemic activity. Patients treated with metformin show a significant mortality reduction and lower progression towards end-stage renal disease in comparison with those treated with other hypoglycemic drugs. Concerning lactic acidosis, in the last few years it has been shown how lactic acidosis almost always developed when patients kept taking the drug in the face of a concomitant disease or situation such as sepsis, fever, diarrhea, vomiting, which reduced metformin renal clearance. Actually, clearance of metformin is mainly renal, both by glomerular filtration and tubular secretion (apparent clearance 933–1317 ml/min, half-life < 3 h). As regards treatment, in cases of lactic acidosis complicated by acute kidney injury, continuous renal replacement therapy (CRRT) plays a crucial role. Besides the elimination of metformin, CRRT improves survival by correcting acidosis, electrolyte alterations, and maintaining fluid balance. Lactic acidosis almost always develops because of preventable drug accumulation. Therefore, prevention is a key factor. Patients should be aware that discontinuation for a limited time does not affect their health, even when it may be inappropriate, but it may avoid a serious, potentially fatal adverse event.
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Affiliation(s)
- Filippo Mariano
- Department of Medical Sciences, University of Turin, Turin, Italy.
| | - Luigi Biancone
- Department of Medical Sciences, University of Turin, Turin, Italy
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37
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Yang Q, Zheng J, Wen D, Chen X, Chen W, Chen W, Xiong X, Zhang Z. Association between metformin use on admission and outcomes in intensive care unit patients with acute kidney injury and type 2 diabetes: A retrospective cohort study. J Crit Care 2020; 62:206-211. [PMID: 33422811 DOI: 10.1016/j.jcrc.2020.12.007] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 12/06/2020] [Accepted: 12/12/2020] [Indexed: 12/12/2022]
Abstract
PURPOSE Acute kidney injury (AKI) occurs in more than half of intensive care unit patients. Effective prevention and treatment strategies for AKI remain limited. We aimed to assess AKI-related mortality in patients with diabetes who were metformin and non-metformin users. MATERIALS AND METHODS We included patients with AKI and type 2 diabetes (T2DM) from the Medical Information Mart for Intensive Care database. The 30-day mortality, neutrophil-to-lymphocyte ratio, and length of hospital stay were compared between patients with and without metformin prescriptions. We used multivariable Cox proportional hazards regression, propensity score analysis, and an inverse probability-weighting model to ensure the robustness of our findings. RESULTS We included 4328 patients with AKI and T2DM (998 and 3330 patients were metformin and non-metformin users, respectively). The overall 30-day mortality was 14.2% (613/4328); it was 15.7% (523/3330) and 9.0% (90/998) for non-metformin and metformin users, respectively. In the inverse probability-weighting model, metformin use was associated with 37% lower 30-day mortality (HR = 0.63, 95% CI: 0.50-0.80, p < 0.0001). CONCLUSIONS Metformin use may be associated with reduced risk-adjusted mortality in patients with AKI and T2DM. Further randomized controlled trials are needed to clarify this association.
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Affiliation(s)
- Qilin Yang
- Department of Critical Care, the Second Affiliated Hospital of Guangzhou Medical University, No. 250 Changgang East Road, Haizhu District, Guangzhou, Guangdong, China.
| | - Jiezhao Zheng
- Department of Critical Care, the Second Affiliated Hospital of Guangzhou Medical University, No. 250 Changgang East Road, Haizhu District, Guangzhou, Guangdong, China.
| | - Deliang Wen
- Department of Critical Care, the Second Affiliated Hospital of Guangzhou Medical University, No. 250 Changgang East Road, Haizhu District, Guangzhou, Guangdong, China.
| | - Xiaohua Chen
- Department of Critical Care, the Second Affiliated Hospital of Guangzhou Medical University, No. 250 Changgang East Road, Haizhu District, Guangzhou, Guangdong, China.
| | - Weiyan Chen
- Department of Critical Care, the Second Affiliated Hospital of Guangzhou Medical University, No. 250 Changgang East Road, Haizhu District, Guangzhou, Guangdong, China.
| | - Weixiao Chen
- Department of Critical Care, the Second Affiliated Hospital of Guangzhou Medical University, No. 250 Changgang East Road, Haizhu District, Guangzhou, Guangdong, China.
| | - Xuming Xiong
- Department of Critical Care, the Second Affiliated Hospital of Guangzhou Medical University, No. 250 Changgang East Road, Haizhu District, Guangzhou, Guangdong, China.
| | - Zhenhui Zhang
- Department of Critical Care, the Second Affiliated Hospital of Guangzhou Medical University, No. 250 Changgang East Road, Haizhu District, Guangzhou, Guangdong, China.
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38
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Elnaem MH, Mansour NO, Nahas AF, Baraka MA, Elkalmi R, Cheema E. Renal Outcomes Associated with the Use of Non-Insulin Antidiabetic Pharmacotherapy: A Review of Current Evidence and Recommendations. Int J Gen Med 2020; 13:1395-1409. [PMID: 33324086 PMCID: PMC7733337 DOI: 10.2147/ijgm.s285191] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2020] [Accepted: 10/12/2020] [Indexed: 01/17/2023] Open
Abstract
Background This study aims to discuss, summarize and compare the renal outcomes associated with non-insulin antidiabetic (AD) pharmacotherapy prescribed for patients with type 2 diabetes mellitus (T2DM). Methods A systematic search using predefined search terms in three scholarly databases, ScienceDirect, Google Scholar, and PubMed, was conducted. Original research articles published in the English language between 2012 and 2020 that reported renal outcomes associated with the use of non-insulin AD pharmacotherapy were eligible for inclusion. Review articles, meta-analysis studies, and conference proceedings were excluded. A study-specific data extraction form was designed to extract the author’s name, country, publication year, study design, study population, objectives, key findings, and conclusions. A narrative review of the key findings that focused on renal outcomes and renal safety issues was conducted. Results Of the 18,872 results identified through the initial search, a total of 32 articles were included in this review. Of these, 18 of the included articles reported the renal outcomes of newer antidiabetic medications, eg, SGLT2 inhibitors and GLP-1 agonists. Eight studies focussed on the well-established antidiabetic medications, eg, metformin and sulphonylureas. The review reported three main types of the clinical impact of the prescribed AD on the renal outcomes: “renoprotective effects”, “no additional risk” and “associated with a decline in renal parameters”. Seventeen studies reported the renoprotective effects of AD, including SGLT2i studies (n=8), GLP1 studies (n=6), and DPP4i studies (n=3). The reported renoprotective effects included slowing down the GFR decline, improving albuminuria, and reducing renal adverse events. The “no additional risk” impact was reported in eight studies, including DPP4i studies (n=3), two SGLT2i studies (n=2), metformin studies (n=2), and one study involving pioglitazone. Furthermore, seven studies highlighted the “associated with a decline in renal parameters” effect. Of these, three involved SGLT2i, two with metformin, and one for each DPP4i and sulphonylurea. Conclusion More than half of the studies included in this review supported the renoprotective effects associated with the use of AD medications, particularly GLP-1A, SGLT2i, and some of the DPP4i. Further studies involving patients with various stages of chronic kidney disease (CKD) are required to compare AD medications’ renal effects, particularly the newer agents.
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Affiliation(s)
- Mohamed Hassan Elnaem
- Department of Pharmacy Practice, Faculty of Pharmacy, International Islamic University Malaysia, Kuantan, Pahang.,Quality Use of Medicines Research Group, Faculty of Pharmacy, International Islamic University Malaysia, Kuantan, Pahang
| | - Noha O Mansour
- Pharmacy Practice Department, Faculty of Pharmacy, Mansoura University, Cairo, Egypt
| | - Abdulrahman Fata Nahas
- Department of Pharmacy Practice, Faculty of Pharmacy, International Islamic University Malaysia, Kuantan, Pahang.,Quality Use of Medicines Research Group, Faculty of Pharmacy, International Islamic University Malaysia, Kuantan, Pahang
| | - Mohamed A Baraka
- Department of Clinical Pharmacy, College of Pharmacy, Al Ain University, Al Ain, United Arab Emirates.,Department of Clinical Pharmacy, College of Pharmacy, Al-Azhar University, Cairo, Egypt
| | - Ramadan Elkalmi
- Department of Clinical Pharmacy and Pharmacotherapeutics, Dubai Pharmacy College, Dubai, United Arab Emirates.,Department of Pharmacology, Faculty of Medicine, Sebha University, Sabha, Libya
| | - Ejaz Cheema
- School of Pharmacy, University of Birmingham, Birmingham B15 2TT, UK
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Hanna RM, Rhee CM, Kalantar-Zadeh K. Metformin in chronic kidney disease: a strong dose of caution. Kidney Int 2020; 98:1101-1105. [PMID: 33126975 DOI: 10.1016/j.kint.2020.04.060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2020] [Revised: 04/19/2020] [Accepted: 04/22/2020] [Indexed: 10/23/2022]
Affiliation(s)
- Ramy M Hanna
- Department of Medicine, Division of Nephrology, University of California Irvine Medical Center, Irvine, California, USA; Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology, Hypertension and Kidney Transplantation, Department of Medicine, University of California Irvine School of Medicine, Orange, California, USA
| | - Connie M Rhee
- Department of Medicine, Division of Nephrology, University of California Irvine Medical Center, Irvine, California, USA; Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology, Hypertension and Kidney Transplantation, Department of Medicine, University of California Irvine School of Medicine, Orange, California, USA; Nephrology Section, Department of Medicine, Veterans Affairs Long Beach Healthcare System, Long Beach, California, USA
| | - Kamyar Kalantar-Zadeh
- Department of Medicine, Division of Nephrology, University of California Irvine Medical Center, Irvine, California, USA; Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology, Hypertension and Kidney Transplantation, Department of Medicine, University of California Irvine School of Medicine, Orange, California, USA; Nephrology Section, Department of Medicine, Veterans Affairs Long Beach Healthcare System, Long Beach, California, USA; Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California, USA.
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40
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Schytz PA, Nissen AB, Hommel K, Schou M, Nelveg-Kristensen KE, Torp-Pedersen C, Gislason GH, Gerds TA, Carlson N. Is metformin associated with acute kidney injury? A case-control study of patients with type 2 diabetes admitted with acute infection. J Nephrol 2020; 34:709-717. [PMID: 33001414 DOI: 10.1007/s40620-020-00863-5] [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: 07/21/2020] [Accepted: 09/14/2020] [Indexed: 11/29/2022]
Abstract
INTRODUCTION Despite the long-term renoprotective effects of Metformin, a recent study on data from the U.S. Food and Drug Administration reported a possible nephrotoxic effect, contributing to the development of acute kidney injury (AKI). We investigated the association between metformin and AKI in patients admitted with the AKI-prone condition of acute infection and compared results with corresponding results of other antidiabetics. METHODS In a nationwide register-based case-control study, we identified Danish patients with type 2 diabetes hospitalized with acute infection between 2008 and 2018. Cases of AKI had an increase in plasma creatinine ≥ × 1.5 during admission, controls did not. Antidiabetics were identified up to 6 months before admission. Odds ratio (OR) of each antidiabetic was computed in separate multiple logistic regression models adjusted for relevant medication and comorbidities and results compared. RESULTS We included 46,811 patients, hereof 9454 AKIs (20%) and 2186 (4.7%) severe AKIs. Overall, 56% were males, median age (IQR) was 73 (65-81). Sixty percent received metformin, 13% sulfonylurea, 31% insulin and 8% dipeptidyl peptidase-4 inhibitors (DPP-4i), with equal distribution between cases and controls. Metformin was associated with increased OR (CI) for AKI, 1.07 (1.02-1.12), equally to sulfonylurea, 1.10 (1.03-1.18) and DPP-4i, 1.11 (1.02-1.20), but not insulin, 0.99 (0.93-1.05). In severe AKI, results for metformin were 1.27 (1.25-1.40) but increased equivalently to other antidiabetics. CONCLUSIONS In patients with type 2 diabetes hospitalized with acute infection, metformin was not independently associated with AKI, since other antidiabetics were also significantly associated, indicating confounding by indication.
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Affiliation(s)
- Philip Andreas Schytz
- Department of Cardiology, Herlev and Gentofte Hospital, Kildegaardsvej 28, 2900, Hellerup, Copenhagen, Denmark.
| | - Anders Bonde Nissen
- Department of Cardiology, Herlev and Gentofte Hospital, Kildegaardsvej 28, 2900, Hellerup, Copenhagen, Denmark
| | - Kristine Hommel
- Department of Medicine, Herlev and Gentofte Hospital, Hellerup, Denmark
| | - Morten Schou
- Department of Cardiology, Herlev and Gentofte Hospital, Kildegaardsvej 28, 2900, Hellerup, Copenhagen, Denmark
| | | | | | - Gunnar H Gislason
- Department of Cardiology, Herlev and Gentofte Hospital, Kildegaardsvej 28, 2900, Hellerup, Copenhagen, Denmark
| | - Thomas A Gerds
- Department of Biostatistics, Copenhagen University, Copenhagen, Denmark
| | - Nicholas Carlson
- Department of Nephrology, The Danish Heart Foundation and Specialist Registrar, Rigshospitalet, Copenhagen, Denmark
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Gao S, Chen Y, Hu R, Lu W, Yu L, Chen J, Liu S, Guo Y, Shen Q, Wang B, Fang W. Visualized analysis and evaluation of simultaneous controlled release of metformin hydrochloride and gliclazide from sandwiched osmotic pump capsule. Drug Dev Ind Pharm 2020; 46:1776-1786. [PMID: 32895014 DOI: 10.1080/03639045.2020.1821047] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
The aim of this study was to develop the Metformin Hydrochloride and Gliclazide (MH-GZ) sandwiched osmotic pump capsule which could overcome the problems associated with short half-life and burst release. The system could deliver drugs with different solubility simultaneously at zero-order rate, in which MH-GZ were filled in both sides of the push layer respectively. The single factor and orthogonal test were employed to obtain the optimized formulation with the evaluation index of similarity factor (ƒ2). R language was used to visualized analyze the main influence factors of drug release and their correlations. Pharmacokinetic study was performed in beagle dogs compared to the marketed conventional product, which showed decreased Cmax, prolonged Tmax, and improved bioavailability, independent of pH and agitational speed but related to osmotic pressure differences across the semi permeable membrane. The designed sandwiched osmotic pump capsule proposed a promising substitute for the marketed product for the treatment of type 2 diabetes.
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Affiliation(s)
- Song Gao
- Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei, Anhui, China
| | - Yanjun Chen
- Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei, Anhui, China.,College of Biotechnology and Pharmaceutical Engineering, West Anhui University, Lu'an, Anhui, China
| | - Rongfeng Hu
- Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei, Anhui, China.,Anhui Province Key Laboratory of Chinese Medicinal Formula, Anhui University of Chinese Medicine, Hefei, Anhui, China.,Anhui Province Key Laboratory of Research and Development of Chinese Medicine, Anhui University of Chinese Medicine, Hefei, Anhui, China.,Anhui Province Key Laboratory of Pharmaceutical Technology and Application, Anhui University of Chinese Medicine, Hefei, Anhui, China
| | - Wenjie Lu
- School of Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China
| | - Lingfei Yu
- Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei, Anhui, China
| | - Jiayi Chen
- Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, New York, NY, USA
| | - Songlin Liu
- Anhui Huangshan Capsule Co., Ltd, Huangshan, Anhui, China
| | - Yuxing Guo
- Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, New York, NY, USA
| | - Qiang Shen
- Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei, Anhui, China
| | - Bin Wang
- Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei, Anhui, China
| | - Wenyou Fang
- Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei, Anhui, China
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Posma RA, Venema LH, Huijink TM, Westerkamp AC, Wessels AMA, De Vries NJ, Doesburg F, Roggeveld J, Ottens PJ, Touw DJ, Nijsten MW, Leuvenink HGD. Increasing metformin concentrations and its excretion in both rat and porcine ex vivo normothermic kidney perfusion model. BMJ Open Diabetes Res Care 2020; 8:8/1/e000816. [PMID: 32816871 PMCID: PMC7437879 DOI: 10.1136/bmjdrc-2019-000816] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2019] [Revised: 05/12/2020] [Accepted: 06/12/2020] [Indexed: 11/25/2022] Open
Abstract
INTRODUCTION Metformin can accumulate and cause lactic acidosis in patients with renal insufficiency. Metformin is known to inhibit mitochondria, while renal secretion of the drug by proximal tubules indirectly requires energy. We investigated whether addition of metformin before or during ex vivo isolated normothermic machine perfusion (NMP) of porcine and rat kidneys affects its elimination. RESEARCH DESIGN AND METHODS First, Lewis rats were pretreated with metformin or saline the day before nephrectomy. Subsequently, NMP of the kidney was performed for 90 min. Metformin was added to the perfusion fluid in one of three different concentrations (none, 30 mg/L or 300 mg/L). Second, metformin was added in increasing doses to the perfusion fluid during 4 hours of NMP of porcine kidneys. Metformin concentration was determined in the perfusion fluid and urine by liquid chromatography-tandem mass spectrometry. RESULTS Metformin clearance was approximately 4-5 times higher than creatinine clearance in both models, underscoring secretion of the drug. Metformin clearance at the end of NMP in rat kidneys perfused with 30 mg/L was lower than in metformin pretreated rats without the addition of metformin during perfusion (both p≤0.05), but kidneys perfused with 300 mg/L trended toward lower metformin clearance (p=0.06). Creatinine clearance was not different between treatment groups. During NMP of porcine kidneys, metformin clearance peaked at 90 min of NMP (18.2±13.7 mL/min/100 g). Thereafter, metformin clearance declined, while creatinine clearance remained stable. This observation can be explained by saturation of metformin transporters with a Michaelis-Menten constant (95% CI) of 23.0 (10.0 to 52.3) mg/L. CONCLUSIONS Metformin was secreted during NMP of both rat and porcine kidneys. Excretion of metformin decreased under increasing concentrations of metformin, which might be explained by saturation of metformin transporters rather than a self-inhibitory effect. It remains unknown whether a self-inhibitory effect contributes to metformin accumulation in humans with longer exposure times.
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Affiliation(s)
- Rene A Posma
- Department of Critical Care, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Leonie H Venema
- Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Tobias M Huijink
- Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Andrie C Westerkamp
- Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - A Mireille A Wessels
- Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Nynke J De Vries
- Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Frank Doesburg
- Department of Critical Care, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - J Roggeveld
- Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Petra J Ottens
- Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Daan J Touw
- Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Maarten W Nijsten
- Department of Critical Care, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Henri G D Leuvenink
- Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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Pan Q, Lu X, Zhao C, Liao S, Chen X, Guo F, Yang C, Liu HF. Metformin: the updated protective property in kidney disease. Aging (Albany NY) 2020; 12:8742-8759. [PMID: 32364526 PMCID: PMC7244070 DOI: 10.18632/aging.103095] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Accepted: 03/30/2020] [Indexed: 12/16/2022]
Abstract
Metformin is a frontline hypoglycemic agent, which is mainly prescribed to manage type 2 diabetes mellitus with obesity. Emerging evidence suggests that metformin also exerts protective effects against various kidney diseases. Some postulate that kidney disease is actually a metabolic disease, accompanied by nonresolving pathophysiologic pathways controlling oxidative stress, endoplasmic reticulum stress, inflammation, lipotoxicity, fibrosis, and senescence, as well as insufficient host defense mechanisms such as AMP-activated protein kinase (AMPK) signaling and autophagy. Metformin may interfere with these pathways by orchestrating AMPK signaling and AMPK-independent pathways to protect the kidneys from injury. Furthermore, the United States Food and Drug Administration declared metformin is safe for patients with mild or moderate kidney impairment in 2016, assuaging some conservative attitudes about metformin management in patients with renal insufficiency and broadening the scope of research on the renal protective effects of metformin. This review focuses on the molecular mechanisms by which metformin imparts renal protection and its potential in the treatment of various kidney diseases.
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Affiliation(s)
- Qingjun Pan
- Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang, Institute of Nephrology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, Guangdong, China
| | - Xing Lu
- Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang, Institute of Nephrology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, Guangdong, China
| | - Chunfei Zhao
- Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang, Institute of Nephrology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, Guangdong, China
| | - Shuzhen Liao
- Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang, Institute of Nephrology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, Guangdong, China
| | - Xiaoqun Chen
- Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang, Institute of Nephrology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, Guangdong, China
| | - Fengbiao Guo
- Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang, Institute of Nephrology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, Guangdong, China
| | - Chen Yang
- Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang, Institute of Nephrology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, Guangdong, China
| | - Hua-Feng Liu
- Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang, Institute of Nephrology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, Guangdong, China
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Kwon S, Kim YC, Park JY, Lee J, An JN, Kim CT, Oh S, Park S, Kim DK, Oh YK, Kim YS, Lim CS, Lee JP. The Long-term Effects of Metformin on Patients With Type 2 Diabetic Kidney Disease. Diabetes Care 2020; 43:948-955. [PMID: 32132005 DOI: 10.2337/dc19-0936] [Citation(s) in RCA: 74] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Accepted: 02/09/2020] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Metformin is the first pharmacological option for treating type 2 diabetes. However, the use of this drug is not recommended in individuals with impaired kidney function because of the perceived risk of lactic acidosis. We aimed to assess the efficacy and safety of metformin in patients with type 2 diabetic kidney disease (DKD). RESEARCH DESIGN AND METHODS We conducted a retrospective observational cohort study of 10,426 patients with type 2 DKD from two tertiary hospitals. The primary outcomes were all-cause mortality and end-stage renal disease (ESRD) progression. The secondary outcome was metformin-associated lactic acidosis. Taking into account the possibility that patients with less severe disease were prescribed metformin, propensity score matching (PSM) was conducted. RESULTS All-cause mortality and incident ESRD were lower in the metformin group according to the multivariate Cox analysis. Because the two groups had significantly different baseline characteristics, PSM was performed. After matching, metformin usage was still associated with lower all-cause mortality (adjusted hazard ratio [aHR] 0.65; 95% CI 0.57-0.73; P < 0.001) and ESRD progression (aHR 0.67; 95% CI 0.58-0.77; P < 0.001). Only one event of metformin-associated lactic acidosis was recorded. In both the original and PSM groups, metformin usage did not increase the risk of lactic acidosis events from all causes (aHR 0.92; 95% CI 0.668-1.276; P = 0.629). CONCLUSIONS In the present retrospective study, metformin usage in advanced chronic kidney disease (CKD) patients, especially those with CKD 3B, decreased the risk of all-cause mortality and incident ESRD. Additionally, metformin did not increase the risk of lactic acidosis. However, considering the remaining biases even after PSM, further randomized controlled trials are needed to change real-world practice.
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Affiliation(s)
- Soie Kwon
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.,Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea
| | - Yong Chul Kim
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - Jae Yoon Park
- Department of Internal Medicine, Dongguk University Ilsan Hospital, Goyang, Korea
| | - Jeonghwan Lee
- Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea
| | - Jung Nam An
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, Gyeonggi-do, Korea
| | - Clara Tammy Kim
- Institute of Life and Death Studies, Hallym University, Chuncheon, Korea
| | - Sohee Oh
- Department of Biostatistics, Seoul Metropolitan Government, Seoul National University Boramae Medical Center, Seoul, Korea
| | - Seokwoo Park
- Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.,Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Dong Ki Kim
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.,Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Yun Kyu Oh
- Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea.,Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Yon Su Kim
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - Chun Soo Lim
- Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea.,Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Jung Pyo Lee
- Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea .,Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
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Huynh K, Baghdanian AH, Baghdanian AA, Sun DS, Kolli KP, Zagoria RJ. Updated guidelines for intravenous contrast use for CT and MRI. Emerg Radiol 2020; 27:115-126. [PMID: 31925592 DOI: 10.1007/s10140-020-01751-y] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2019] [Accepted: 01/03/2020] [Indexed: 12/29/2022]
Abstract
Intravenous (IV) contrast material is used extensively for CT and MRI scans done in emergency departments (ED). Its use is essential to make many critical diagnoses in ED patients. While adverse reactions can occur, newer research has added to our knowledge of IV contrast media tolerance and safety leading to improved and more liberal guidelines for intravenous contrast use. The updated information described in this review article indicates how intravenous contrast can be used safely in more patients, more expeditiously and with fewer precautions than with prior guidelines. This review article explains the basis for the new recommendations for intravenous contrast material use and describes indicated precautions and preparations to avoid adverse reactions for iodinated agents used for CT and gadolinium agents for MRI.
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Affiliation(s)
- Kevin Huynh
- Department of Radiology and Biomedical Imaging, University of California San Francisco, 505 Parnassus Ave, San Francisco, CA, 94143, USA
| | - Arthur H Baghdanian
- Department of Radiology, University of Southern California, 1975 Zonal Ave, Los Angeles, CA, 90033, USA
| | - Armonde A Baghdanian
- Department of Radiology, University of Southern California, 1975 Zonal Ave, Los Angeles, CA, 90033, USA
| | - Derek S Sun
- Department of Radiology and Biomedical Imaging, University of California San Francisco, 505 Parnassus Ave, San Francisco, CA, 94143, USA
| | - K Pallav Kolli
- Department of Radiology and Biomedical Imaging, University of California San Francisco, 505 Parnassus Ave, San Francisco, CA, 94143, USA.
| | - Ronald J Zagoria
- Department of Radiology and Biomedical Imaging, University of California San Francisco, 505 Parnassus Ave, San Francisco, CA, 94143, USA
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Abstract
Metformin is a widely used biguanide drug due to its safety and low cost. It has been used for over 60 years to treat type 2 diabetes at the early stages because of its outstanding ability to decrease plasma glucose levels. Over time, different uses of metformin were discovered, and the benefits of metformin for various diseases and even aging were verified. These diseases include cancers (e.g., breast cancer, endometrial cancer, bone cancer, colorectal cancer, and melanoma), obesity, liver diseases, cardiovascular disease, and renal diseases. Metformin exerts different effects through different signaling pathways. However, the underlying mechanisms of these different benefits remain to be elucidated. The aim of this review is to provide a brief summary of the benefits of metformin and to discuss the possible underlying mechanisms.
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Affiliation(s)
- Ziquan Lv
- Department of Molecular Epidemiology, Shenzhen Center for Disease Control and Prevention, Shenzhen, China
| | - Yajie Guo
- The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China
- *Correspondence: Yajie Guo
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Salvatore T, Pafundi PC, Marfella R, Sardu C, Rinaldi L, Monaco L, Ricozzi C, Imbriani S, Nevola R, Adinolfi LE, Sasso FC. Metformin lactic acidosis: Should we still be afraid? Diabetes Res Clin Pract 2019; 157:107879. [PMID: 31618624 DOI: 10.1016/j.diabres.2019.107879] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2019] [Revised: 09/27/2019] [Accepted: 10/11/2019] [Indexed: 12/11/2022]
Abstract
Metformin, the first choice drug for type 2 diabetes treatment in all stages of therapy, and one of the most widely prescribed anti-hyperglycemic agents worldwide, represents a rare example of an old drug which continues to display new beneficial effects in various fields. However, lactic acidosis (LA) persists as a serious adverse effect. LA incidence is low and is not necessarily determined by the administration of metformin. Unfortunately, the concern for this complication has negatively affected the drug use, particularly in chronic kidney disease, which may impair drug excretion, and in congestive heart failure and chronic liver disease, which may promote lactate accumulation. This review describes how not only these historical contraindications have been considerably scaled back, though rather a recent large body of evidence supports a protective effect of biguanide on kidney, heart and liver and, maybe, against lactic acidosis itself. It is worthy to slow down both contraindications and precautions to metformin use, not to deprive a significant number of diabetic patients, as those with kidney, heart and liver comorbidities, from its potential benefits, and not to hamper in the near future the putative advantages in a wide spectrum of conditions outside of diabetes.
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Affiliation(s)
- Teresa Salvatore
- Unit of Internal Medicine, Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Piazza Miraglia, 2, 80138 Naples, Italy.
| | - Pia Clara Pafundi
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Piazza Miraglia, 2, 80138 Naples, Italy.
| | - Raffaele Marfella
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Piazza Miraglia, 2, 80138 Naples, Italy.
| | - Celestino Sardu
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Piazza Miraglia, 2, 80138 Naples, Italy.
| | - Luca Rinaldi
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Piazza Miraglia, 2, 80138 Naples, Italy.
| | - Lucio Monaco
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Piazza Miraglia, 2, 80138 Naples, Italy.
| | - Carmen Ricozzi
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Piazza Miraglia, 2, 80138 Naples, Italy.
| | - Simona Imbriani
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Piazza Miraglia, 2, 80138 Naples, Italy.
| | - Riccardo Nevola
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Piazza Miraglia, 2, 80138 Naples, Italy.
| | - Luigi Elio Adinolfi
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Piazza Miraglia, 2, 80138 Naples, Italy.
| | - Ferdinando Carlo Sasso
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Piazza Miraglia, 2, 80138 Naples, Italy.
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Corchia A, Wynckel A, Journet J, Moussi Frances J, Skandrani N, Lautrette A, Zafrani L, Lewandowski E, Reboul P, Vrigneaud L, Djerada Z, Rieu P. Metformin-related lactic acidosis with acute kidney injury: results of a French observational multicenter study. Clin Toxicol (Phila) 2019; 58:375-382. [DOI: 10.1080/15563650.2019.1648816] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Affiliation(s)
| | | | - Julien Journet
- Department of Nephrology, William Morey Hospital, Chalon-sur-Saône, France
| | - Julie Moussi Frances
- Department of Nephrology, APHM Hôpital de la Conception, CHU Marseille, Marseille, France
| | - Nihel Skandrani
- Department of Nephrology, Belfort Montbéliard Hospital, Montbéliard, France
| | | | - Lara Zafrani
- Intensive Care Unit, Hôpital Saint Louis, Paris, France
| | | | | | - Laurence Vrigneaud
- Department of Internal Medicine & Nephrology, Valenciennes Hospital, Valenciennes, France
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Corremans R, Vervaet BA, D'Haese PC, Neven E, Verhulst A. Metformin: A Candidate Drug for Renal Diseases. Int J Mol Sci 2018; 20:E42. [PMID: 30583483 PMCID: PMC6337137 DOI: 10.3390/ijms20010042] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2018] [Revised: 12/12/2018] [Accepted: 12/20/2018] [Indexed: 12/11/2022] Open
Abstract
Over the past decades metformin has been the optimal first-line treatment for type 2 diabetes mellitus (T2DM). Only in the last few years, it has become increasingly clear that metformin exerts benign pleiotropic actions beyond its prescribed use and ongoing investigations focus on a putative beneficial impact of metformin on the kidney. Both acute kidney injury (AKI) and chronic kidney disease (CKD), two major renal health issues, often result in the need for renal replacement therapy (dialysis or transplantation) with a high socio-economic impact for the patients. Unfortunately, to date, effective treatment directly targeting the kidney is lacking. Metformin has been shown to exert beneficial effects on the kidney in various clinical trials and experimental studies performed in divergent rodent models representing different types of renal diseases going from AKI to CKD. Despite growing evidence on metformin as a candidate drug for renal diseases, in-depth research is imperative to unravel the molecular signaling pathways responsible for metformin's renoprotective actions. This review will discuss the current state-of-the-art literature on clinical and preclinical data, and put forward potential cellular mechanisms and molecular pathways by which metformin ameliorates AKI/CKD.
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Affiliation(s)
- Raphaëlle Corremans
- Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, 2000 Antwerp, Belgium.
| | - Benjamin A Vervaet
- Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, 2000 Antwerp, Belgium.
| | - Patrick C D'Haese
- Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, 2000 Antwerp, Belgium.
| | - Ellen Neven
- Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, 2000 Antwerp, Belgium.
| | - Anja Verhulst
- Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, 2000 Antwerp, Belgium.
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50
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Welch HK, Kellum JA, Kane-Gill SL. Drug-Associated Acute Kidney Injury Identified in the United States Food and Drug Administration Adverse Event Reporting System Database. Pharmacotherapy 2018; 38:785-793. [PMID: 29883524 DOI: 10.1002/phar.2152] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
STUDY OBJECTIVE Acute kidney injury (AKI) is a common condition associated with both short-term and long-term consequences including dialysis, chronic kidney disease, and mortality. Although the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database is a powerful tool to examine drug-associated events, to our knowledge, no study has analyzed this database to identify the most common drugs reported with AKI. The objective of this study was to analyze AKI reports and associated medications in the FAERS database. DESIGN Retrospective pharmacovigilance disproportionality analysis. DATA SOURCE Food and Drug Administration Adverse Event Reporting System database. MEASUREMENTS AND MAIN RESULTS We queried the FAERS database for reports of AKI from 2004 quarter 1 through 2015 quarter 3. Extracted drugs were assessed using published references and categorized as known, possible, or new potential nephrotoxins. The reporting odds ratio (ROR), a measure of reporting disproportionality, was calculated for the 20 most frequently reported drugs in each category. We retrieved 7,241,385 adverse event reports, of which 193,996 (2.7%) included a report of AKI. Of the AKI reports, 16.5% were known nephrotoxins, 18.6% were possible nephrotoxins, and 64.8% were new potential nephrotoxins. Among the most commonly reported drugs, those with the highest AKI ROR were aprotinin (7614 reports; ROR 115.70, 95% confidence interval [CI] 110.63-121.01), sodium phosphate (1687 reports; ROR 55.81, 95% CI 51.78-60.17), furosemide (1743 reports; ROR 12.61, 95% CI 11.94-13.32), vancomycin (1270 reports, ROR 12.19, 95% CI 11.45-12.99), and metformin (4701 reports; ROR 10.65, 95% CI 10.31-11.00). The combined RORs for the 20 most frequently reported drugs with each nephrotoxin classification were 3.71 (95% CI 3.66-3.76) for known nephrotoxins, 2.09 (95% CI 2.06-2.12) for possible nephrotoxins, and 1.55 (95% CI 1.53-1.57) for new potential nephrotoxins. CONCLUSION Acute kidney injury was a common reason for adverse event reporting in the FAERS. Most AKI reports were generated for medications not recognized as nephrotoxic according to our classification system. This report provides data on medications needing further research to determine the risk of AKI with these new potential nephrotoxins.
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Affiliation(s)
- Hanna K Welch
- Department of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania
| | - John A Kellum
- Center for Critical Care Nephrology, The CRISMA (Clinical Research, Investigation, and Systems Modeling of Acute Illness) Center, Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Sandra L Kane-Gill
- Department of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania.,Department of Critical Care Medicine, Biomedical Informatics, and Clinical Translational Science Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
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