Clinical journal of the American Society of Nephrology : CJASN · 2025
Combining Ketoacid Analog Supplemented Low-Protein Diets with Sodium-Glucose Cotransporter-2 Inhibitors for Patients with Diabetic Kidney Disease.
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Yen Chieh-Li, Fan Pei-Chun, Lee Cheng-Chia, Chen Jia-Jin, Lu Yueh-An, Tu Yi-Ran, Chu Pao-Hsien, Hsiao Ching-Chung, Chen Yung-Chang, Chang Chih-Hsiang
Аннотация
KEY POINTS: The combined effect of sodium-glucose cotransporter-2 inhibitors (SGLT2is) and KA-AA–supplemented low-protein diets has rarely been studied. This cohort included 1729 type 2 diabetes mellitus patients with eGFR ≤30 ml/min per 1.73 m2 who newly received KA-AA supplemented low protein diet (sLPD), with or without SGLT2is. The combination of SGLT2is and KA-AA sLPD is linked to lower all-cause and cardiovascular disease mortality than KA-AA sLPD alone.
BACKGROUND: The combination of a supplemented low protein diet (sLPD) with ketoacid analogs and amino acids (KA-AA)—which has been shown to be safe for patients with diabetic kidney disease in some previous studies—and the antidiabetic sodium-glucose cotransporter-2 inhibitors (SGLT2is)—known for their cardiovascular and kidney-protective effects—may represent a treatment strategy for patients with advanced diabetic kidney disease. However, this combination has rarely been investigated in previous studies.
METHODS: This retrospective cohort study included a total of 1729 adult patients with type 2 diabetes mellitus with an eGFR ≤30 ml/min per 1.73 m2 and newly received sLPD treatment. We then divided the patients into two groups on the basis of whether they received a combination of KA-AA and SGLT2is (combination group) or KA-AA alone (KA-AA group). Inverse probability of treatment weighting was performed to balance baseline characteristics.
RESULTS: At the 3-year follow-up, compared with the KA-AA group, the combination group exhibited significantly lower risks of all-cause death (16% versus 27%; hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.61 to 0.87), composite of all-cause death and ESKD (54% versus 63%; subdistribution HR, 0.84; 95% CI, 0.75 to 0.93), and cardiovascular death (7% versus 12%; subdistribution HR, 0.68; 95% CI, 0.52 to 0.89). The risk of new-onset ESKD requiring dialysis and heart failure–related hospitalization did not significantly differ.
CONCLUSIONS: These findings suggest that the addition of SGLT2is to KA-AA sLPD is associated with lower all-cause and cardiovascular mortality.
BACKGROUND: The combination of a supplemented low protein diet (sLPD) with ketoacid analogs and amino acids (KA-AA)—which has been shown to be safe for patients with diabetic kidney disease in some previous studies—and the antidiabetic sodium-glucose cotransporter-2 inhibitors (SGLT2is)—known for their cardiovascular and kidney-protective effects—may represent a treatment strategy for patients with advanced diabetic kidney disease. However, this combination has rarely been investigated in previous studies.
METHODS: This retrospective cohort study included a total of 1729 adult patients with type 2 diabetes mellitus with an eGFR ≤30 ml/min per 1.73 m2 and newly received sLPD treatment. We then divided the patients into two groups on the basis of whether they received a combination of KA-AA and SGLT2is (combination group) or KA-AA alone (KA-AA group). Inverse probability of treatment weighting was performed to balance baseline characteristics.
RESULTS: At the 3-year follow-up, compared with the KA-AA group, the combination group exhibited significantly lower risks of all-cause death (16% versus 27%; hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.61 to 0.87), composite of all-cause death and ESKD (54% versus 63%; subdistribution HR, 0.84; 95% CI, 0.75 to 0.93), and cardiovascular death (7% versus 12%; subdistribution HR, 0.68; 95% CI, 0.52 to 0.89). The risk of new-onset ESKD requiring dialysis and heart failure–related hospitalization did not significantly differ.
CONCLUSIONS: These findings suggest that the addition of SGLT2is to KA-AA sLPD is associated with lower all-cause and cardiovascular mortality.