Furthermore, in post hoc parallel trial analyses of PARADIGM-HF and PARAGON-HF (the prospective comparison of ARNI with ARB global outcomes in HFpEF) [49, 53], continuation of ARNI did not increase the risk of deterioration in kidney function in HF patients who had an eGFR < 30 mL/min/1.73 m2 at least once in follow-up compared with renin–angiotensin system inhibitor (p > 0.05) [66]. This evidence concerns the gene REN and hydrops fetalis.