Low-Protein Diets and Its Synergistic Role in the SGLT2 Inhibitor Era

Low-protein diets (LPDs), usually defined as a daily dietary protein intake of 0.6 to 0.8 g/kg body weight, have been recommended for decades as a safe and effective lifestyle modification to ameliorate inflammatory damage and proteinuria, reduce glomerular hyperfiltration, and improve metabolic acidosis control in patients with chronic kidney disease (CKD). The mechanism for this is largely attributed to altered tubuloglomerular feedback and afferent arteriole contraction leading to decreased glomerular pressure. Additionally, low protein intake reduces urea generation, which can help delay dialysis initiation in advanced CKD. LPDs have different types including plant-dominant LPDs that can exert additional kidney protective effects as a result of dietary protein quality in addition to quantity. In addition, strong clinical evidence shows that a new class of diabetes mellitus medications, the sodium-glucose cotransporter 2 inhibitors, reduces albuminuria and slows the estimated glomerular filtration rate decline in CKD, even in patients without diabetes mellitus, especially if significant proteinuria is present. Given prior studies investigating the effect of LPDs used in conjunction with angiotensin pathway modulators, we argue that LPDs have a synergistic role in disease management and are expected to display additive effects when combined with sodium-glucose cotransporter 2 inhibitor usage or other pharmacologic agents. Even with medical therapy, it is prudent to implement tailored LPDs for different types of CKD.