In the Renal Optimization Strategies Evaluation–Acute Heart Failure (ROSE-HF) trial, protocol-driven aggressive diuresis caused worsening of renal function (WRF), based on ≥ 20% decrease in eGFR using cystatin C, in 21% of participants but was not associated with an increase in kidney tubular injury markers (29). This evidence concerns the gene CST3 and hydrops fetalis.