Long-term effects of ketoanalogues on mortality and progression to dialysis in predialysis CKD stage 5 patients: A nationwide population-based study

Introduction: Ketoanalogues (KA)–supplemented very low protein diet can defer dialysis initiation in patients with stage 4 and 5 chronic kidney disease stage (CKD).However, the effects of KA supplement on mortality and the progression to dialysis in predialysis CKD stage 5 patients with low protein diet is inconclusive.

Material and methods:Using the original claims of one million individuals of Taiwan’s National Health Insurance database between 1996 and 2011, 165 predialysis advanced CKD patients on low protein diet (0.6 g/kg/day) with KA supplement were enrolled and were matched with 165 predialysis advanced CKD patients on low protein diet without KA supplement by age, gender, and duration of predialysis advanced CKD. Cox proportional-hazards regression analysis was used to evaluate mortality and the progression to dialysis.

Results: Of the 165 advanced CKD patients who received KA, 34 patients (20.6%) died and 124 patients (75.2%) underwent long-term dialysis during the study period. There was no statistically significant difference in mortality between the KA-user group and the KA-nonuser group. Administering KA to advanced CKD patients significantly increased the long-term dialysis risk (adjusted hazard ratio [HR], 1.41; 95% confidence interval [CI], 1.04–1.90) and the combined outcome risk, defined as long-term dialysis or death, (adjusted HR, 1.37; 95% CI, 1.02–1.83). Additionally, KA supplementation increased the long-term dialysis risk (adjusted HR, 1.49; 95% CI, 1.00–2.20) in a subgroup of advanced CKD patients with diabetes mellitus (DM), but not in advanced CKD patients without DM. 

Conclusion: KA supplementation may increase the risk of long-term dialysis in predialysis advanced CKD patients who are receiving low-protein diets, and this risk also exists in the subgroup of advanced CKD patients with DM.