A Low-Protein Diet for Diabetic Kidney Disease: Its Effect and Molecular Mechanism, an Approach from Animal Studies

Abstract

A low-protein diet (LPD) can be expected to retard renal function decline in advanced stages of chronic kidney disease (CKD), including diabetic kidney disease (DKD), and is recommended in a clinical setting. Regarding the molecular mechanisms of an LPD against DKD, previous animal studies have shown that an LPD exerts reno-protection through mainly the improvement of glomerular hyperfiltration/hypertension due to the reduction of intraglomerular pressure. On the other hand, we have demonstrated that an LPD, particularly a very-LPD (VLPD), improved tubulo-interstitial damage, inflammation and fibrosis, through the restoration of autophagy via the reduction of a mammalian target of rapamycin complex 1 (mTORC1) activity in type 2 diabetes and obesity animal models. Thus, based on animal studies, a VLPD may show a more beneficial effect against advanced DKD. Previous clinical reports have also shown that a VLPD, not a moderate LPD, slows the progression of renal dysfunction in patients with chronic glomerular nephritis. However, there is insufficient clinical data regarding the beneficial effects of a VLPD against DKD. Additionally, the patients with CKD, including DKD, are a high-risk group for malnutrition, such as protein–energy wasting (PEW), sarcopenia, and frailty. Therefore, an LPD, including a VLPD, should be prescribed to patients when the benefits of an LPD outweigh the risks, upon consideration of adherence, age, and nutritional status. As the future predicts, the development of a VLPD replacement therapy without malnutrition may be expected for reno-protection against the advanced stages of DKD, through the regulation of mTORC1 activity and adequate autophagy induction. However, further studies to elucidate detailed mechanisms by which a VLPD exerts reno-protection are necessary.

Diabetic Kidney Disease Benefits from Intensive Low-Protein Diet: Updated Systematic Review and Meta-analysis

“…A sustained LPD dilates the efferent arterioles and decreases intraglomerular pressure, leading to an improvement in GFR. In addition, a lower intake of dietary protein results in inhibition of the glomerular hyperfiltration-stimulated mesangial-cell signaling that leads to increased transforming growth factor β release and subsequent progressive fibrosis and, ultimately, renal inflammation [ 32 ]. Importantly, LPD can be synergistic with the direct effect of a low-sodium diet as well as the effect of angiotensin pathway inhibition [ 8 ].…”

Dietary Protein Intake, Protein Energy Wasting, and the Progression of Chronic Kidney Disease: Analysis from the KNOW-CKD Study

“…Ever since the MDRD study failed to prove the benefits of an LPD to postpone CKD progression [11], the use of an LPD as an important treatment option in patients with CKD has been doubtful. Nonetheless, numerous studies have been conducted to compensate the failure of the MDRD study because consumption of an LPD is hypothetically excellent [35]. In this regard, a recent study by Garneata et al, successfully revisited the clinical usefulness of LPD consumption to delay CKD progression [20].…”

Decreased Bioimpedance Phase Angle in Patients with Diabetic Chronic Kidney Disease Stage 5

“…However, there is still controversy as to the relative advantages and disadvantages of limiting protein intake to prevent the progression of CKD without causing protein energy wasting [12]. Nutritional therapy, which can prevent the deterioration of kidney function in patients with DMCKD, and even better control of blood sugar, blood pressure, and lipid profile, are also very important [13].…”