Genetically predicted adiponectin causally reduces the risk of chronic kidney disease, a bilateral and multivariable mendelian randomization study

Wu, Ruicheng; Luo, Peiyi; Luo, Min; Li, Xiaoyü; Zhong, Xin; He, Qiang; Zhang, Jie; Zhang, Yangchang; Xiong, Yang; Han, Ping

doi:10.3389/fgene.2022.920510

Cited by 3 publications

(2 citation statements)

References 34 publications

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“… 49 A high leptin-adiponectin ratio is associated with CKD, 49 and adiponectin reduces CKD risk. 50 SGLT2-inhibitors significantly decrease leptin and increase adiponectin levels in clinical trials involving patients with type 2 diabetes. 51 Mechanisms underlying these findings have not been fully elucidated.…”

Section: Optimization Of Kidney's Energy Substrate Utilization and De...mentioning

confidence: 94%

SGLT2 Inhibitors and Kidney Protection: Mechanisms Beyond Tubuloglomerular Feedback

Upadhyay

2024

Kidney360

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Sodium-glucose cotransporter 2 (SGLT2)-inhibitors reduce the risk for kidney failure and are a key component of guideline-directed therapy for chronic kidney disease. While SGLT2-inhibitors’ ability to activate tubulo-glomerular feedback and reduce hyperfiltration-mediated kidney injury is considered to be the central mechanism for kidney protection, recent data from experimental studies raises questions on the primacy of this mechanism. This review examines SGLT2-inhibitors’ role in tubulo-glomerular feedback and summarizes emerging evidence on following of SGLT2-inhibitors’ other putative mechanisms for kidney protection: optimization of kidney’s energy substrate utilization and delivery, regulation of autophagy and maintenance of cellular homeostasis, attenuation of sympathetic hyperactivity, and improvement in vascular health and microvascular function. It is imperative to examine the impact of SGLT2 inhibition on these different physiologic processes to help our understanding of mechanisms underpinning kidney protection with this important class of drugs.

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Section: Optimization Of Kidney's Energy Substrate Utilization and De...mentioning

confidence: 94%

SGLT2 Inhibitors and Kidney Protection: Mechanisms Beyond Tubuloglomerular Feedback

Upadhyay

2024

Kidney360

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“…The observed increase in adiponectin may be the result of kidney damage rather than the cause of kidney function injury. Nonetheless, adiponectin has been shown to improve insulin sensitivity and maintain homeostasis, which may be a mechanism underlying its protective effect on kidney function [ 47 ]. Moreover, low birth weight has been associated with an increased risk of CKD.…”

Section: Lifestyle Factors and Renal Functionmentioning

confidence: 99%

Recent advances in the application of Mendelian randomization to chronic kidney disease

Wen,

Chen,

Jia

et al. 2024

Renal Failure

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Objective Chronic kidney disease (CKD) is a condition influenced by both genetic and environmental factors and has been a focus of extensive research. Utilizing Mendelian randomization, researchers have begun to untangle the complex causal relationships underlying CKD. This review delves into the advances and challenges in the application of MR in the field of nephrology, shifting from a mere summary of its principles and limitations to a more nuanced exploration of its contributions to our understanding of CKD. Methods Key findings from recent studies have been pivotal in reshaping our comprehension of CKD. Notably, evidence indicates that elevated testosterone levels may impair renal function, while higher sex hormone-binding globulin (SHBG) levels appear to be protective, predominantly in men. Surprisingly, variations in plasma glucose and glycated hemoglobin levels seem unaffected by genetically induced changes in the estimated glomerular filtration rate (eGFR), suggesting an independent pathway for renal function impairment. Results Furthermore, lifestyle factors such as physical activity and socioeconomic status emerge as significant influencers of CKD risk and kidney health. The relationship between sleep duration and CKD is nuanced; short sleep duration is linked to increased risk, while long sleep duration does not exhibit a clear causal effect. Additionally, lifestyle factors, including diet, exercise, and mental wellness activities, play a crucial role in kidney health. New insights also reveal a substantial causal connection between both central and general obesity and CKD onset, while no significant links were found between genetically modified LDL cholesterol or triglyceride levels and kidney function. Conclusion This review not only presents the recent achievements of MR in CKD research but also illuminates the path forwards, underscoring critical unanswered questions and proposing future research directions in this dynamic field.

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Association of Thyroid-Stimulating Hormone With All-Cause Mortality: A 2-Sample Mendelian Randomization Study

Song

et al. 2023

The Journal of Clinical Endocrinology &Amp; Metabolism

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Background Thyroid-stimulating hormone (TSH), as the most sensitive and specific marker of thyroid status, is associated with multiple health outcomes, including mortality. However, whether TSH levels are causally associated with the risk of mortality remain unclear. This study aims to investigate the causal association between TSH levels and all-cause mortality using Mendelian randomization (MR) analyses. Methods MR analyses using single-nucleotide polymorphisms (SNPs) associated with TSH levels (P < 5 × 10−8) as instruments. Mortality data were obtained from the UK Biobank, including 384,344 participants who were recruited from 22 assessment centers across the UK taken between 2006 and 2010. Cox proportional hazards regression was used to estimate the association of the TSH genetic risk score (GRS) with all-cause and cause-specific mortality. Results 15,557 individuals died during a median of 9.00 years of follow-up in the UK Biobank. A total of 70 SNPs were included in the MR analysis. The main MR analyses showed that one standard deviation increase in TSH was associated with a decreased risk of all-cause mortality (OR: 0.972, 95%CI: 0.948-0.996), which may be largely attributed to respiratory diseases mortality (OR: 0.881, 95%CI: 0.805-0.963). The multivariable HRs(95%CIs) of all-cause mortality across three TSH GRS categories were 1.00(reference), 0.976(0.940-1.014), and 0.947(0.911-0.985), respectively (P for trend < 0.01). Moreover, except digestive diseases mortality, genetically predicted TSH levels were negatively associated with mortality from CVD, cancer, non-cancer, and dementia, although not statistically significant. Conclusions Higher TSH levels were causally associated with lower risk of all-cause mortality which may be largely attributed to respiratory diseases mortality.

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Genetically predicted adiponectin causally reduces the risk of chronic kidney disease, a bilateral and multivariable mendelian randomization study

Cited by 3 publications

References 34 publications

SGLT2 Inhibitors and Kidney Protection: Mechanisms Beyond Tubuloglomerular Feedback

SGLT2 Inhibitors and Kidney Protection: Mechanisms Beyond Tubuloglomerular Feedback

Recent advances in the application of Mendelian randomization to chronic kidney disease

Association of Thyroid-Stimulating Hormone With All-Cause Mortality: A 2-Sample Mendelian Randomization Study

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