The Effect of Ketoanalogues on Chronic Kidney Disease Deterioration: A Meta-Analysis

Abstract

The effects of ketoanalogues (KA) on chronic kidney disease (CKD) deterioration have not yet been fully confirmed. To strengthen the evidence of the role of KA in CKD, PubMed and Embase were searched for studies published through February 2019. Effect sizes from ten randomized control trials (RCTs) and two non-RCTs comprising a total of 951 patients were pooled and analyzed. A restricted protein diet supplemented with ketoanalogues (RPKA) was found to significantly delay the progression of CKD (p = 0.008), particularly in patients with an estimated glomerular filtration rate (eGFR) > 18 mL/min/1.73 m2 (p < 0.0001). No significant change in eGFR was found when comparing a very-low-protein diet and a low-protein diet (p = 0.10). In addition, compared with the placebo, RPKA did not cause malnutrition (albumin: p = 0.56; cholesterol: p = 0.50). Moreover, RPKA significantly decreased phosphorous levels (p = 0.001), increased calcium levels (p = 0.04), and decreased parathyroid hormone (PTH) levels (p = 0.05) in patients with eGFR < 18 mL/min/1.73 m2. In conclusion, RPKA could slow down the progression of CKD in patients with eGFR > 18 mL/min/1.73 m2 without causing malnutrition and reverse CKD-MBD in patients with eGFR < 18 mL/min/1.73 m2.

Long-Term Effects of Ketoanalogues on Mortality and Renal Outcomes in Advanced Chronic Kidney Disease Patients Receiving a Low-Protein Diet

“…However, this study design has raised concerns of immortal time bias because they compared KA use periods and their countermanded KA use periods of the same individual as a period without KA treatment. Additionally, their result was not supported by a recent meta-analysis study conducted by Li et al, who examined the effects of KA on CKD deterioration [10]. Four studies (394 patients) were included in the subgroup of eGFR <18 mL/min per 1.73 m 2 , and four studies (267 patients) were included in the subgroup of eGFR >18 mL/min/1.73 m 2 .…”

“…The effects of KA on patients with advanced CKD with an LPD are unclear [8][9][10][11]. Wu et al conducted a retrospective cohort study in which 1483 anemic patients with advanced CKD receiving an LPD (0.8 g/kg/day) plus KA for 180 days were included [9].…”

“…Studies have demonstrated that the benefits of ketoanalogues (KA) supplementation on mortality and renal outcomes in CKD patients undergoing dietary protein restriction are controversial [7][8][9][10][11]. First, regarding the effects of KA supplementation through a VLPD on patients with stage 4 and 5 CKD, Garneata et al conducted a prospective randomized controlled trial in 207 patients with estimated glomerular filtration rate (eGFR) < 30 mL/min and noted that KA supplementation with a vegetarian VLPD (0.3 g/kg body weight/day) could defer dialysis initiation compared with an LPD (0.6 g/kg body weight/day) alone [7].…”

“…First, regarding the effects of KA supplementation through a VLPD on patients with stage 4 and 5 CKD, Garneata et al conducted a prospective randomized controlled trial in 207 patients with estimated glomerular filtration rate (eGFR) < 30 mL/min and noted that KA supplementation with a vegetarian VLPD (0.3 g/kg body weight/day) could defer dialysis initiation compared with an LPD (0.6 g/kg body weight/day) alone [7]. However, the effects of KA supplementation with an LPD on patients with stage 5 CKD were inconclusive [8][9][10][11]. A study with only 45 patients reported no significant difference in the rate of decline of renal function between non-dialytic stage 5 CKD patients with an LPD (0.6-0.8 g/kg/day) plus KA supplementation for six months and those with an LPD alone [8].…”

“…Besides, according to a recent meta-analysis, a subgroup analysis of a restricted protein diet showed that an LPD with KA supplementation could prevent renal function deterioration compared with LPD alone in patients with eGFR >18 mL/min/1.73 m 2 , but there was no data from patients with eGFR <18 mL/min/1.73 m 2 . Because the efficacy of protein-restricted regimens remained unclear [10], the feasibility and compliance of patients to the LPD were repeatedly questioned and reported as poorly obeyed, and the risk of malnutrition was frequently raised [15][16][17][18]. Therefore, we conducted this study to evaluate the long-term effects of KA on mortality and renal outcomes in patients with pre-dialysis stage 5 CKD (advanced CKD) who received an LPD.…”