Although guideline-directed medical therapies, including RAAS inhibitors, beta-adrenergic receptor blockers (beta-blockers), mineralocorticoid receptor antagonists (MRAs), and sodium-glucose cotransporter-2 (SGLT-2) inhibitors improve outcomes in HF, their use in advanced CKD is limited by safety concerns and lack of trial data. This evidence concerns the gene SLC5A2 and hydrops fetalis.