Talk Description
435R - Research Paper
Abstract
Aim:
This study employs a drug-target Mendelian randomisation (MR) approach1 in the general population to investigate the effect of cardiometabolic drugs for improving kidney function.
Method:
We identified single nucleotide polymorphisms as proxies for anti-hypertensive (Ca-channel blockers, beta-blockers, ACE inhibitors); anti-diabetic (SGLT2-inhibitors, metformin); and cholesterol-lowering (evolo-/alirocumab, statins, and ezetimibe) drug targets. Their intermediate effects on systolic blood pressure, HbA1c, and low-density lipoprotein (LDL) cholesterol level were used as exposures, while the outcome was annual decline of creatinine-based estimated glomerular filtration rate (eGFR) in 343339 individuals (74% European ancestry)2. We implemented several two-sample MR methods (inverse variance weighted, weighted median, weighted mode, MR-Egger).
Results:
A one standard deviation (SD) unit reduction in HbA1c (6.75 mmol/mol) via SGLT2 (target of SGLT2-inhibitors) caused an improvement in annual eGFR by ϐ=0.40 (95%CI 0.22; 0.59). A one SD reduction in LDL cholesterol (38.7 mg/dL) via PCSK9 (target of evolo-/alirocumab) decreased annual eGFR by ϐ=-0.07 (95%CI -0.13; -0.02). Inference for antihypertensive drug targets was inconclusive.
Conclusion:
Our study underscores the potential of SGLT2-inhibitors in preserving kidney function. The effect of decreasing eGFR was specific to evolo-/alirocumab but not the other cholesterol-lowering drugs. The results support personalized treatment for cardiometabolic patients at risk of kidney impairment. Further studies are required to validate results in CKD cases. 1 Burgess, et.al. https://doi.org/10.1016/j.ajhg.2022.12.0172 Gorski, et.al. https://doi.org/10.1016/j.kint.2022.05.021
Abstract
Aim:
This study employs a drug-target Mendelian randomisation (MR) approach1 in the general population to investigate the effect of cardiometabolic drugs for improving kidney function.
Method:
We identified single nucleotide polymorphisms as proxies for anti-hypertensive (Ca-channel blockers, beta-blockers, ACE inhibitors); anti-diabetic (SGLT2-inhibitors, metformin); and cholesterol-lowering (evolo-/alirocumab, statins, and ezetimibe) drug targets. Their intermediate effects on systolic blood pressure, HbA1c, and low-density lipoprotein (LDL) cholesterol level were used as exposures, while the outcome was annual decline of creatinine-based estimated glomerular filtration rate (eGFR) in 343339 individuals (74% European ancestry)2. We implemented several two-sample MR methods (inverse variance weighted, weighted median, weighted mode, MR-Egger).
Results:
A one standard deviation (SD) unit reduction in HbA1c (6.75 mmol/mol) via SGLT2 (target of SGLT2-inhibitors) caused an improvement in annual eGFR by ϐ=0.40 (95%CI 0.22; 0.59). A one SD reduction in LDL cholesterol (38.7 mg/dL) via PCSK9 (target of evolo-/alirocumab) decreased annual eGFR by ϐ=-0.07 (95%CI -0.13; -0.02). Inference for antihypertensive drug targets was inconclusive.
Conclusion:
Our study underscores the potential of SGLT2-inhibitors in preserving kidney function. The effect of decreasing eGFR was specific to evolo-/alirocumab but not the other cholesterol-lowering drugs. The results support personalized treatment for cardiometabolic patients at risk of kidney impairment. Further studies are required to validate results in CKD cases. 1 Burgess, et.al. https://doi.org/10.1016/j.ajhg.2022.12.0172 Gorski, et.al. https://doi.org/10.1016/j.kint.2022.05.021