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      Mechanisms and Efficacy of Chinese Herbal Medicines in Chronic Kidney Disease

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          Abstract

          As the current treatment of chronic kidney disease (CKD) is limited, it is necessary to seek more effective and safer treatment methods, such as Chinese herbal medicines (CHMs). In order to clarify the modern theoretical basis and molecular mechanisms of CHMs, we reviewed the knowledge based on publications in peer-reviewed English-language journals, focusing on the anti-inflammatory, antioxidative, anti-apoptotic, autophagy-mediated and antifibrotic effects of CHMs commonly used in kidney disease. We also discussed recently published clinical trials and meta-analyses in this field. Based on recent studies regarding the mechanisms of kidney disease in vivo and in vitro, CHMs have anti-inflammatory, antioxidative, anti-apoptotic, autophagy-mediated, and antifibrotic effects. Several well-designed randomized controlled trials (RCTs) and meta-analyses demonstrated that the use of CHMs as an adjuvant to conventional medicines may benefit patients with CKD. Unknown active ingredients, low quality and small sample sizes of some clinical trials, and the safety of CHMs have restricted the development of CHMs. CHMs is a potential method in the treatment of CKD. Further study on the mechanism and well-conducted RCTs are urgently needed to evaluate the efficacy and safety of CHMs.

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          Chronic Kidney Disease.

          The definition and classification of chronic kidney disease (CKD) have evolved over time, but current international guidelines define this condition as decreased kidney function shown by glomerular filtration rate (GFR) of less than 60 mL/min per 1·73 m(2), or markers of kidney damage, or both, of at least 3 months duration, regardless of the underlying cause. Diabetes and hypertension are the main causes of CKD in all high-income and middle-income countries, and also in many low-income countries. Incidence, prevalence, and progression of CKD also vary within countries by ethnicity and social determinants of health, possibly through epigenetic influence. Many people are asymptomatic or have non-specific symptoms such as lethargy, itch, or loss of appetite. Diagnosis is commonly made after chance findings from screening tests (urinary dipstick or blood tests), or when symptoms become severe. The best available indicator of overall kidney function is GFR, which is measured either via exogenous markers (eg, DTPA, iohexol), or estimated using equations. Presence of proteinuria is associated with increased risk of progression of CKD and death. Kidney biopsy samples can show definitive evidence of CKD, through common changes such as glomerular sclerosis, tubular atrophy, and interstitial fibrosis. Complications include anaemia due to reduced production of erythropoietin by the kidney; reduced red blood cell survival and iron deficiency; and mineral bone disease caused by disturbed vitamin D, calcium, and phosphate metabolism. People with CKD are five to ten times more likely to die prematurely than they are to progress to end stage kidney disease. This increased risk of death rises exponentially as kidney function worsens and is largely attributable to death from cardiovascular disease, although cancer incidence and mortality are also increased. Health-related quality of life is substantially lower for people with CKD than for the general population, and falls as GFR declines. Interventions targeting specific symptoms, or aimed at supporting educational or lifestyle considerations, make a positive difference to people living with CKD. Inequity in access to services for this disease disproportionally affects disadvantaged populations, and health service provision to incentivise early intervention over provision of care only for advanced CKD is still evolving in many countries.
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            Chronic kidney disease: global dimension and perspectives.

            Chronic kidney disease is defined as a reduced glomerular filtration rate, increased urinary albumin excretion, or both, and is an increasing public health issue. Prevalence is estimated to be 8-16% worldwide. Complications include increased all-cause and cardiovascular mortality, kidney-disease progression, acute kidney injury, cognitive decline, anaemia, mineral and bone disorders, and fractures. Worldwide, diabetes mellitus is the most common cause of chronic kidney disease, but in some regions other causes, such as herbal and environmental toxins, are more common. The poorest populations are at the highest risk. Screening and intervention can prevent chronic kidney disease, and where management strategies have been implemented the incidence of end-stage kidney disease has been reduced. Awareness of the disorder, however, remains low in many communities and among many physicians. Strategies to reduce burden and costs related to chronic kidney disease need to be included in national programmes for non-communicable diseases. Copyright © 2013 Elsevier Ltd. All rights reserved.
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              Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis.

              Substantial controversy surrounds the use of estimated glomerular filtration rate (eGFR) and albuminuria to define chronic kidney disease and assign its stages. We undertook a meta-analysis to assess the independent and combined associations of eGFR and albuminuria with mortality. In this collaborative meta-analysis of general population cohorts, we pooled standardised data for all-cause and cardiovascular mortality from studies containing at least 1000 participants and baseline information about eGFR and urine albumin concentrations. Cox proportional hazards models were used to estimate hazard ratios (HRs) for all-cause and cardiovascular mortality associated with eGFR and albuminuria, adjusted for potential confounders. The analysis included 105,872 participants (730,577 person-years) from 14 studies with urine albumin-to-creatinine ratio (ACR) measurements and 1,128,310 participants (4,732,110 person-years) from seven studies with urine protein dipstick measurements. In studies with ACR measurements, risk of mortality was unrelated to eGFR between 75 mL/min/1.73 m(2) and 105 mL/min/1.73 m(2) and increased at lower eGFRs. Compared with eGFR 95 mL/min/1.73 m(2), adjusted HRs for all-cause mortality were 1.18 (95% CI 1.05-1.32) for eGFR 60 mL/min/1.73 m(2), 1.57 (1.39-1.78) for 45 mL/min/1.73 m(2), and 3.14 (2.39-4.13) for 15 mL/min/1.73 m(2). ACR was associated with risk of mortality linearly on the log-log scale without threshold effects. Compared with ACR 0.6 mg/mmol, adjusted HRs for all-cause mortality were 1.20 (1.15-1.26) for ACR 1.1 mg/mmol, 1.63 (1.50-1.77) for 3.4 mg/mmol, and 2.22 (1.97-2.51) for 33.9 mg/mmol. eGFR and ACR were multiplicatively associated with risk of mortality without evidence of interaction. Similar findings were recorded for cardiovascular mortality and in studies with dipstick measurements. eGFR less than 60 mL/min/1.73 m(2) and ACR 1.1 mg/mmol (10 mg/g) or more are independent predictors of mortality risk in the general population. This study provides quantitative data for use of both kidney measures for risk assessment and definition and staging of chronic kidney disease. Kidney Disease: Improving Global Outcomes (KDIGO), US National Kidney Foundation, and Dutch Kidney Foundation. Copyright 2010 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                29 March 2021
                2020
                : 11
                : 619201
                Affiliations
                [ 1 ]Department of Nephrology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
                [ 2 ]Beijing University of Chinese Medicine, Beijing, China
                [ 3 ]Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
                [ 4 ]NMPA Key Laboratory for Clinical Research and Evaluation of Traditional Chinese Medicine, Beijing, China
                [ 5 ]National Clinical Research Center for Chinese Medicine Cardiology, Beijing, China
                Author notes

                Edited by: Jianping Chen, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, China

                Reviewed by: Dâmaris Silveira, University of Brasilia, Brazil

                Yaoguang Wang, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, China

                *Correspondence: Hua Qu, hua_qu@ 123456yeah.net ; Yu Zhang, zhangyu8225@ 123456126.com
                [†]

                These authors have contributed equally to this work and share first authorship

                This article was submitted to Ethnopharmacology, a section of the journal Frontiers in Pharmacology

                Article
                619201
                10.3389/fphar.2020.619201
                8039908
                33854427
                66f01d08-0543-4ce4-9ea0-bf8e26e51bcf
                Copyright © 2021 Zhao, Yu, Wang, Chang, Ma, Qu and Zhang.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 19 October 2020
                : 17 December 2020
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Award ID: 81873300
                Funded by: Capital Health Research and Development of Special 10.13039/501100010270
                Award ID: 2018-2-4173
                Categories
                Pharmacology
                Review

                Pharmacology & Pharmaceutical medicine
                chronic kidney disease,chinese herbal medicines,anti-inflammatory,antioxidative,anti-apoptotic,autophagy-mediated,antifibrotic

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