Prevention Of Kidney Disease Research Articles

Discussion on the treatment of diabetic kidney disease based on the "gut-fat-kidney" axis.

Diabetic kidney disease is the main cause of end-stage renal disease, and its prevention and treatment are still a major clinical problem. The human intestine has a complex flora of hundreds of millions of microorganisms, and intestinal microorganisms, and their derivatives are closely related to renal inflammatory response, immune response, and material metabolism. Brown adipose tissue is the main part of adaptive thermogenesis. Recent studies have shown that activating brown fat by regulating intestinal flora has good curative effects in diabetic kidney disease-related diseases. As an emerging medical concept, the "gut-fat-kidney" axis has received increasing attention in diabetic kidney disease and related diseases. However, the specific mechanism involved needs further study. A new theoretical basis for the prevention and treatment of diabetic kidney disease is presented in this article, based on the "gut-fat-kidney" axis.

Renal endowment in men and women: start from the beginning.

The development of the human kidney leads to the establishment of nephron endowment through a process influenced by both genetic and environmental factors. There is individual variability regarding nephron endowment and factors including aging and pathological conditions contribute to the decline in the number of nephrons, impacting renal function. Genetic determinants, such as mutations in crucial developmental genes like Pax2, and epigenetic mechanisms mediated by key enzymes including sirtuin 3, play critical roles in the regulation of the number of nephrons, with implications for kidney disease susceptibility. Sexual dimorphism significantly influences kidney development and function, with the number of nephrons being significantly lower in females, consistent with lower female birth weight, which is considered a surrogate for nephron endowment. Also, although females have fewer nephrons, they experience a slower decline in GFR compared to males. Gender disparity in chronic kidney disease progression has been attributed to factors such as metabolism, oxidative stress, renal hemodynamics, and sex hormones. Understanding the complexities of nephron endowment variability, genetic determinants, and sexual dimorphism in kidney development and function is crucial for elucidating the mechanisms underlying individual kidney disease susceptibility and progression. Further research in this field holds promise for the development of personalized approaches to kidney disease prevention, management, and treatment.

GWAS Meta-analysis of Kidney Function Traits in Japanese Populations.

Genetic epidemiological evidence for the kidney function traits in East Asian populations, including Japanese, remain still relatively unclarified. Especially, the number of genome-wide association studies (GWASs) for kidney traits reported still remains limited, and the sample size of each independent study is relatively small. Given the genetic variability between ancestries/ethnicities, implementation of GWAS with sufficiently large sample sizes in specific population of Japanese is considered meaningful. We conducted the GWAS meta-analyses of kidney traits by leveraging the GWAS summary data of the representative large genome cohort studies with about 200,000 Japanese participants (n = 202,406 for estimated glomerular filtration rate [eGFR] and n = 200,845 for serum creatinine [SCr]). In the present GWAS meta-analysis, we identified 110 loci with 169 variants significantly associated with eGFR (on chromosomes 1-13 and 15-22; P < 5 × 10-8), whereas we also identified 112 loci with 176 variants significantly associated with SCr (on chromosomes 1-22; P < 5 × 10-8), of which one locus (more than 1 Mb distant from known loci) with one variant (CD36 rs146148222 on chromosome 7) for SCr was considered as the truly novel finding. The present GWAS meta-analysis of the largest genome cohort studies in Japanese subjects provided some original genomic loci associated with kidney function, which may contribute to the possible development of personalized prevention of kidney diseases based on genomic information in the near future.

Discovery and prioritization of genetic determinants of kidney function in 297,355 individuals from Taiwan and Japan

Current genome-wide association studies (GWAS) for kidney function lack ancestral diversity, limiting the applicability to broader populations. The East-Asian population is especially under-represented, despite having the highest global burden of end-stage kidney disease. We conducted a meta-analysis of multiple GWASs (n = 244,952) on estimated glomerular filtration rate and a replication dataset (n = 27,058) from Taiwan and Japan. This study identified 111 lead SNPs in 97 genomic risk loci. Functional enrichment analyses revealed that variants associated with F12 gene and a missense mutation in ABCG2 may contribute to chronic kidney disease (CKD) through influencing inflammation, coagulation, and urate metabolism pathways. In independent cohorts from Taiwan (n = 25,345) and the United Kingdom (n = 260,245), polygenic risk scores (PRSs) for CKD significantly stratified the risk of CKD (p < 0.0001). Further research is required to evaluate the clinical effectiveness of PRSCKD in the early prevention of kidney disease.

Obesity, kidney and metabolic bariatric surgery: a surgeon’s narrative review

Excess body weight impacts kidney function in individuals with severe obesity, primarily through metabolic alterations in adipocytes, especially in visceral adipose tissue. The relationship between persistent sterile inflammation associated with obesity and the progression of obesity-related kidney disease to chronic kidney disease (CKD) is an area of growing interest. The beneficial effects of weight loss on the prevention of kidney disease and the improvement of kidney function in individuals with obesity have been well documented. Currently, the most effective weight loss strategy is metabolic bariatric surgery (MBS), which has been proven to not only prevent the progression of CKD but also reverse it. However, awareness and understanding of the impact of obesity on the kidney should also extend to the severely obese population with clinically normal renal function. The purpose of this review is to outline the current knowledge on the pathophysiology of obesity-induced kidney damage, the effects of MBS on renal function in severely obese individuals with or without CKD, and provide the current evidence on perioperative management strategies for CKD patients, including diet and nutrition.

ACE Inhibitors and Angiotensin Receptor Blockers for the Primary and Secondary Prevention of Cardiovascular Outcomes: Recommendations from the 2024 Egyptian Cardiology Expert Consensus in Collaboration with the CVREP Foundation.

The renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in regulating blood pressure (BP), with dysregulation of RAAS resulting in hypertension and potentially heart failure (HF), myocardial infarction (MI), cardio-renal syndrome, and stroke. RAAS inhibitors, such as angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs), have advantages beyond BP control. However, differences between these two drug classes need to be considered when choosing a therapy for preventing cardiovascular events. A panel of 36 Egyptian cardiologists developed consensus statements on RAAS inhibitors for primary and secondary prevention of cardiovascular outcomes and stroke, using a modified three-step Delphi process. The consensus statements highlight the importance of effective BP control and the role of RAAS blockade for prevention and management of various cardiovascular diseases. ACEis and ARBs differ in their mode of action and, thus, clinical effects. On the basis of available evidence, the consensus group recommended the following: ACEis should be considered as first choice (in preference to ARBs) to reduce the risk of MI, for primary prevention of HF, and for secondary prevention of stroke. ACEis and ARBs show equivalent efficacy for the primary prevention of stroke. Evidence also favors the preferential use of ACEis in patients with type 2 diabetes, for BP control, for the primary prevention of diabetic kidney disease, and to reduce the risk of major cardiovascular and renal outcomes. Treatment with an ACEi should be started within 24 h of ST segment elevation MI (and continued long term) in patients with HF, left ventricular systolic dysfunction, and/or diabetes. Angiotensin receptor/neprilysin inhibitors (ARNIs) are the first choice for patients with HF and reduced ejection fraction, with ACEis being the second choice in this group. ARBs are indicated as alternatives in patients who cannot tolerate ACEis. ACEis may be associated with cough development, but the incidence tends to be overestimated, and the risk can be reduced by use of a lipophilic ACEi or combining the ACEi with a calcium channel blocker. RAAS blockade is an essential component of hypertension therapy; however, the protective effects provided by ACEis are superior to those of ARBs. Therefore, an ACEi is indicated in almost all cases, unless not tolerated.

Individualized treatment of diabetes mellitus in older adults.

The population of older adults with diabetes mellitus is growing but heterogeneous. Because geriatric syndromes, comorbidity or multimorbidity, the complexity of glucose dynamics, and socioeconomic conditions are associated with the risk of severe hypoglycemia and mortality, these factors should be considered in individualized diabetes treatment. Because cognitive impairment and frailty have similar etiologies and risk factors, a common strategy can be implemented to address them through optimal glycemic control, management of vascular risk factors, diet, exercise, social participation, and support. To prevent frailty or sarcopenia, optimal energy intake, adequate protein and vitamin intake, and resistance or multi-component exercise are recommended. For hypoglycemic drug therapy, it is important to reduce hypoglycemia, to use sodium glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, taking into account the benefits for cardiovascular disease and the risk of adverse effects, and to simplify treatment to address poor adherence. Glycemic control goals for older adults with diabetes should be set according to three categories, based on cognitive function and activities of daily living, using the Dementia Assessment Sheet for Community-based Integrated Care System 8-items. This categorization can be used to determine treatment strategies for diabetes when combined with the Comprehensive Geriatric Assessment (CGA). Based on the CGA, frailty prevention, treatment simplification, and social participation or services should be implemented for patients in Category II and above. Measures against hypoglycemia and for the prevention of cardiovascular disease and chronic kidney disease should also be promoted. Treatment based on categorization and CGA by multidisciplinary professionals would be an individualized treatment for older adults with diabetes. Geriatr Gerontol Int 2024; ••: ••-••.

Association between the oxidative balance score and estimated glomerular filtration rate: 2007–2018 NHANES

Oxidative stress is closely associated with the estimated glomerular filtration rate (eGFR) levels. A comprehensive indicator for evaluating dietary and lifestyle exposures to oxidative stress is the Oxidative Balance Score (OBS), with higher OBS suggesting more substantial antioxidant exposures. The aim of this study is to explore the relationship between OBS and eGFR levels. A total of 20,285 subjects were selected from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018. One-way and multifactorial linear regression analyses were used to assess the association of OBS with eGFR. The relationship between OBS and eGFR levels was also assessed using restricted cubic splines (RCS) analysis. OBS levels were significantly and positively correlated with eGFR levels, and eGFR values were more susceptible to OBS in males than in females. Our findings suggest that higher OBS scores may be associated with higher eGFR levels, highlighting the importance of adhering to an antioxidant diet and lifestyle, which can help prevent kidney disease.

Advocacy for DOHaD research optimizing child kidney health

Emerging antenatal risk factors have been associated with an increased risk of kidney disease throughout the offspring's life course. However, the intricate kidney programming mechanisms underlying these risks remain complex and are incompletely understood, but they are rooted in structural and functional alterations within the kidneys. The Developmental Origins of Health and Disease (DOHaD) theory underscores the significance of elucidating core mechanisms initiated through the maternal-fetal interface, which trigger kidney programming. Furthermore, it offers a promising avenue for preventing kidney disease at its earliest stages through a process known as reprogramming. This concise review aims to synthesize existing knowledge regarding the impact of kidney programming on offspring kidney disease and to provide an overview of documented reprogramming strategies as observed in animal models of kidney programming. By consolidating this information, we aim to expedite the translation of research breakthroughs into practical clinical solutions, ultimately resulting in enhanced outcomes for children facing kidney-related issues.

Glucose-Lowering Drugs and Primary Prevention of Chronic Kidney Disease in Type 2 Diabetes Patients: A Real-World Primary Care Study

Background/Objectives: The burden of chronic kidney disease (CKD) is increasing, as is the prevalence of type 2 diabetes mellitus (T2DM). Post-hoc analyses of clinical trials support that sodium–glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptors agonists (GLP-1RAs) prevent CKD in T2DM patients. Methods: We used the Spanish primary care database BIFAP to perform a retrospective cohort study with a nested case-control analysis to assess the incidence, risk factors, and the effect of glucose-lowering drugs (GLDs) on the primary prevention of CKD. Results: From a cohort of 515,701 T2DM subjects (2.75 million person-years), we found 89,075 incident CKD cases, yielding an overall incidence rate (95%CI) of 324.3 (322.1–326.5) per 10,000 person-years. In the nested case–control analysis, gout, hyperuricemia, and hyperkalemia were the factors showing the highest AORs. Long-term users (≥3 years) of GLP1-RAs and SGLT-2i, compared to other GLDs, showed a decreased risk for CKD (AOR = 0.85; 95%CI: 0.73–0.99 and AOR = 0.89; 95%CI: 0.74–1.08, respectively), and for incident CKD at KDIGO stages G3-G5 (AOR = 0.72; 95%CI: 0.56–0.94 and AOR = 0.64; 95%CI: 0.46–0.91, respectively). Conclusions: In a real-world primary care setting, the long-term use of GLP-1RAs and SGLT-2i, but not other GLDs, appeared to decrease the risk of incident CKD in T2DM, supporting a role in primary prevention of CKD.

Plant-based diets for kidney disease prevention and treatment.

Plant-based diets are associated with a lower risk of hypertension, diabetes, cardiovascular disease, and mortality. Using the most recent evidence, we critically appraised the role of plant-based diets in primary and secondary prevention of chronic kidney disease (CKD) with a focus on key nutritional factors (dietary acid load, phosphorus, potassium, sodium, and fiber). In healthy individuals, observational studies found that greater intake of plant protein and higher adherence to plant-based diets (overall, healthful, and provegetarian) was associated with a lower risk of CKD. In those with CKD, plant-based diets were associated with a lower risk of mortality, improved kidney function, and favorable metabolic profiles (fibroblast growth factor-23, uremic toxins, insulin sensitivity, inflammatory biomarkers). Only few studies reported nutrient content of plant-based diets. These studies found that plant-based diets had lower dietary acid load, lower or no significant difference in phosphorus and sodium, and higher potassium and fiber. One study reported that vegetarian diets were associated with severe vitamin D deficiency compared to nonvegetarian diets. Plant-based diets provide several benefits for prevention and management of CKD, with little risk for individuals with CKD. Incorporation of vitamin D rich foods in plant-based diets may be helpful.

The role of SIRT1 in kidney diseases.

SIRT1, a nicotinamide adenine dinucleotide (NAD +)-dependent class III histone deacetylase, exhibits a high level of expression within renal tissues. It has garnered considerable recognition for its pivotal role in modulating signaling pathways intricately linked with the aging process; however, it extends beyond this in the organism. The literature reports that SIRT1 regulates biological processes such as glucose metabolism, lipid metabolism, oxidative stress, inflammation, autophagy, endoplasmic reticulum stress, and apoptosis. Therefore, our study reviews the primary mechanisms by which SIRT1 induces kidney disease and the regulation of related signaling pathways in different models of renal disease. We also discuss commonly studied SIRT1-targeted interventional drugs reported in the literature, including inhibitors (e.g., Ex-527) and activators (e.g., resveratrol). This study aims to provide theoretical foundations and clinical insights for the development and screening of clinical drugs targeting SIRT1, aiming at enhanced scientific approaches for the prevention and treatment of kidney diseases.

In silico medicine and -omics strategies in nephrology: contributions and relevance to the diagnosis and prevention of chronic kidney disease.

Chronic kidney disease (CKD) has been increasing over the last years, with a rate between 0.49% to 0.87% new cases per year. Currently, the number of affected people is around 850 million worldwide. CKD is a slowly progressive disease that leads to irreversible loss of kidney function, end-stage kidney disease, and premature death. Therefore, CKD is considered a global health problem, and this sets the alarm for necessary efficient prediction, management, and disease prevention. At present, modern computer analysis, such as in silico medicine (ISM), denotes an emergent data science that offers interesting promise in the nephrology field. ISM offers reliable computer predictions to suggest optimal treatments in a case-specific manner. In addition, ISM offers the potential to gain a better understanding of the kidney physiology and/or pathophysiology of many complex diseases, together with a multiscale disease modeling. Similarly, -omics platforms (including genomics, transcriptomics, metabolomics, and proteomics), can generate biological data to obtain information on gene expression and regulation, protein turnover, and biological pathway connections in renal diseases. In this sense, the novel patient-centered approach in CKD research is built upon the combination of ISM analysis of human data, the use of in vitro models, and in vivo validation. Thus, one of the main objectives of CKD research is to manage the disease by the identification of new disease drivers, which could be prevented and monitored. This review explores the wide-ranging application of computational medicine and the application of -omics strategies in evaluating and managing kidney diseases.

Knowledge, attitude and practices towards prevention and early detection of chronic kidney disease and associated factors in Ethiopia: A cross-sectional study.

Early detection of chronic kidney disease (CKD) is important because it enables clinicians to initiate effective treatment, preventing loss of kidney function, and delaying or avoiding progression to kidney failure. This study was aimed to assess knowledge, attitude, and practices towards prevention and early detection of CKD and associated factors. Institution based cross-sectional survey was done at Adama Hospital Medical College, Ethiopia, between November 24/2021 and December 24/2021 among 190 hypertensive patients. Data were entered into EpiData version 4.2.0.0 and analyzed by Statistical Package for Social Sciences (SPSS) version 23. The level of good knowledge, positive attitude, and good practice was 40.5%, 53.7%, and 47.4%, respectively. Government employed (AOR = 3.30, 95%CI: 1.38, 7.90), having an average monthly income of ≥3000 ETB (61.43 US dollars) (AOR = 2.95, 95%CI: 1.31, 6.66), and having a duration of ≥4 years since diagnosis of hypertension (AOR = 2.37, 95%CI: 1.11, 5.06) were factors significantly associated with good knowledge. Government employed (AOR = 2.56, 95%CI: 1.12, 5.87), having duration of hypertension ≥4 years since diagnosis (AOR = 2.16, 95%CI: 1.07, 4.36) were factors significantly associated with positive attitude. Government employed (AOR = 4.16, 95%CI: 1.38, 12.58), having an average monthly income of ≥3000 ETB (61.43 US dollars) (AOR = 6.74, 95%CI: 2.93, 15.52), having good knowledge towards prevention and early detection of CKD (AOR = 2.57, 95%CI: 1.14, 5.80) were significantly associated with good practice. The level of good knowledge, positive attitude, and good practice towards was low. Educational programs on these issues are required to minimize the burdens.

Prevention of Chronic Kidney Disease and Its Complications in Older Adults.

In an era marked by a global demographic shift towards an aging society, there is a heightened prevalence of chronic kidney disease (CKD) among older adults. The burden of CKD spans from kidney-related complications to impacting psychological well-being, giving rise to depressive symptoms and caregiver burnout. This article delves into CKD prevention strategies within the context of aging, contributing to the discourse by exploring its multifaceted aspects. The prevention of CKD in the older adults necessitates a comprehensive approach. Primary prevention is centered on the modification of risk factors, acknowledging the intricate interplay of various comorbidities. Secondary prevention focuses on early CKD identification. Tertiary prevention aims to address factors contributing to CKD progression and complications, emphasizing the importance of timely interventions. This comprehensive strategy aims to enhance the quality of life for individuals affected by CKD, decelerating the deterioration of functional status. By addressing CKD at multiple levels, this approach seeks to effectively and compassionately care for the aging population.

921-P: Real-World Study of the Efficacy of an Adjunctive Use of Ipragliflozin for Prevention of Chronic Kidney Disease in People with Type 1 Diabetes (IPRA-CKD)—A Multicenter Retrospective Study

921-P: Real-World Study of the Efficacy of an Adjunctive Use of Ipragliflozin for Prevention of Chronic Kidney Disease in People with Type 1 Diabetes (IPRA-CKD)—A Multicenter Retrospective Study

Remnant cholesterol, preinflammatory state and chronic kidney disease: association and mediation analyses

Blood lipid management is a key approach in the prevention of chronic kidney disease (CKD). Remnant cholesterol (RC) plays an important role in the development of multiple diseases via chronic inflammation. The aim of our study was to determine the relationship between RC and CKD and explore the role of inflammation in this relationship. The 7696 subjects from the Chinese Health and Nutrition Survey were divided into four subgroups according to the quartile of RC. The estimated glomerular filtration rate was calculated using the CKD Epidemiology Collaboration equation. Fasting RC was calculated as total cholesterol minus low-density lipoprotein cholesterol and high-density lipoprotein cholesterol. Logistic regression analysis was employed to evaluate the relationships between RC and CKD. Mediation analysis was undertaken to identify potential mediators of high-sensitivity C-reactive protein (hs-CRP) and white blood cells (WBCs). Of all participants, the mean age was 51 years, and the male accounted for 47.8%. The multivariable-adjusted odds ratios (95% CIs) for the highest versus lowest quartile of remnant cholesterol were 1.40 (1.10–1.78, p for trend = 0.006) for CKD. RC and preinflammatory markers have combined effect on CKD. The preinflammatory state, presented by increased hs-CRP or WBCs, partially mediated the association between RC and CKD with proportion of 10.14% (p = 0.002) and 11.65% (p = 0.012), respectively. In conclusion, this study suggested a positive relationship between RC and CKD, which was partially mediated by preinflammatory state. These findings highlight the importance of RC and inflammation in renal dysfunction. IMPACT STATEMENT What is already known on this subject?: Dyslipidemia plays an important role in the development of chronic kidney disease (CKD). Remnant cholesterol (RC), as a triglyceride-rich particle, can contribute to target organ damage, primarily through inflammatory pathways. However, the relationship between RC and CKD in the community-dwelling population, particularly the role of inflammation, is not yet fully understood. What do the results of this study add?: This study shows that RC was significantly associated with CKD. RC and preinflammatory status exhibit a combined effect on CKD. Preinflammatory state, presented by increased high-sensitivity C-reactive protein or white blood cells, partially mediated the association between RC and CKD. What are the implications of these findings for clinical practice and/or further research?: The study provides us with a better understanding of the role of RC and inflammation in kidney dysfunction and raises the awareness of RC in the management of CKD.

#1895 Elucidating Asprosin's role as an intracellular metabolism regulator in diabetes and obesity-induced renal damage

Abstract Background and Aims Asprosin, an adipokine with a multifaceted function that encompasses inducing insulin resistance, promoting inflammation, and stimulating appetite, is the focus of our investigation. We seek to establish its pivotal role as a mediator in regulating cellular energy metabolism, particularly in the context of renal damage induced by diabetes and obesity. Method We conducted experiments using type 2 diabetic db/db mice and obesity-induced high-fat diet mice. These animal models were categorized into two groups: one received Asprosin neutralizing antibodies (250 μg/mouse/21 days), targeting the 28-amino acid peptide located proximal to Asprosin's C-terminus (KKKELNQLEDRYDKDYLSGELGDNLKMK), while the other received an AMPK activator (Metformin) associated with the regulation of Asprosin receptors (OLFR734/G proteins-cAMP-PKA). Additionally, we cultured renal constituent cells (mesangial cells, glomerular endothelial cells) in high glucose and palmitic acid conditions and silencing Asprosin expression using siRNA. We assessed the levels of Asprosin, AMPK, and their respective downstream signaling pathways. Results Asprosin was found to be overexpressed in the serum and kidney tissues of both db/db mice and high-fat diet mice, as well as in renal constituent cells cultured under high glucose and palmitic acid conditions. Interfering with Asprosin led to reduced body and liver weight in mice, improved glucose tolerance, and mitigated renal injury in vivo. Asprosin knockdown ameliorated lipid accumulation and inflammatory infiltration, both in vitro and in vivo. Moreover, Asprosin absence activated the AMPK/Sirts/mTOR signaling pathway, while the AMPK activator Metformin reversed the effects of Asprosin on lipid accumulation and inflammatory response, confirming Asprosin's direct role in intracellular lipid metabolism. Conclusion The mechanism of intracellular energy metabolism regulation mediated by Asprosin presents promising potential for targeted organ therapy in the development and prevention of diabetic kidney disease. Inhibiting Asprosin suppressed lipid accumulation and inflammation in diabetic kidney disease through the activation of AMPK-associated signaling pathway.

Targeting the sympathetic nervous system with the selective imidazoline receptor agonist moxonidine for the management of hypertension: an international position statement.

Hypertension is often linked with metabolic risk factors that share common pathophysiological pathways. Despite wide-spread availability of multiple drug classes, optimal blood pressure (BP) control remains challenging. Increased central sympathetic outflow is frequently neglected as a critical regulator of both circulatory and metabolic pathways and often remains unopposed therapeutically. Selective imidazoline receptor agonists (SIRAs) effectively reduce BP with a favorable side effect profile compared with older centrally acting antihypertensive drugs. Hard outcome data in hypertension, such as prevention of stroke, heart and kidney diseases, are not available with SIRAs. However, in direct comparisons, SIRAs were as effective as angiotensin-converting enzyme inhibitors, β-blockers, calcium channel blockers, and diuretics in lowering BP. Other beneficial effects on metabolic parameters in hypertensive patients with concomitant overweight and obesity have been documented with SIRAs. Here we review the existing evidence on the safety and efficacy of moxonidine, a widely available SIRA, compared with common antihypertensive agents and provide a consensus position statement based on inputs from 12 experts from Europe and Australia on SIRAs in hypertension management.

Ginsenoside Rg1 attenuates chronic inflammation-induced renal fibrosis in mice by inhibiting AIM2 inflammasome in an Nrf2-dependent manner

Chronic kidney disease (CKD) is a growing global public health issue. Ginsenoside Rg1 (Rg1) has favorable nephroprotective effects, but its role and mechanism in CKD need further investigation. Therefore, we observed the effect of Rg1 on the mouse kidneys after 21 days of low-dose lipopolysaccharide (LPS) exposure. Meanwhile, we investigated the protective mechanism of Rg1 in LPS-induced mesangial cells using the Nrf2 inhibitor ML385. We found that chronic exposure to LPS caused fibrosis in mouse kidneys, accompanied by AIM2 activation and oxidative stress imbalance; however, Rg1 restored the anomalies, accompanied by activation of Nrf2/HO-1 signaling. Finally, our in vitro studies revealed that Rg1′s nephroprotective effects could be inhibited by ML385, and Rg1 can bind Nrf2, suggesting that the protective effects of Rg1 may involve Nrf2 activation and then inhibition of the AIM2. Our study has significant implications for the prevention and treatment of kidney diseases, particularly those related to inflammation.