Patients with systemic-to-pulmonary shunts (i.e., left-to-right) can suffer from glomerular or tubular injury due to reduced systemic blood flow, renal hypoperfusion, and activation of sympathetic and renin–angiotensin–aldosterone systems, resulting in arterial vasoconstriction, fluid and salt retention, volume overload, heart failure, and eventually renal injury [35]. The gene discussed is REN; the disease is heart failure.