Ketoanalogue-Supplemented Low-Protein Diet in Patients with Stage 4+ Chronic Kidney Disease in Italy: A Cost-Utility...

Background/Objectives: Chronic kidney disease (CKD) is associated with substantial clinical and economic burden, largely driven by progression to dialysis. Nutritional interventions have shown potential in delaying disease progression, yet evidence on their cost-effectiveness remains limited. This study evaluated the long-term cost-utility profile of a low-protein diet supplemented with ketoanalogues (s-LPD) versus a standard low-protein diet (LPD) in patients with stage 4+ CKD from both the Italian National Health System (NHS) and societal perspectives. Methods: A Markov model with monthly cycles simulated disease progression from pre-dialysis to dialysis or death. Clinical inputs were derived from the published literature, while costs reflected 2024 Italian tariffs. Three effectiveness scenarios (optimistic, conservative, and pessimistic) were explored to account for uncertainty in the treatment effect. Outcomes included costs, life-years, quality-adjusted life-years (QALYs), and incremental cost-utility ratios. Deterministic and probabilistic sensitivity analyses assessed model robustness. Results: Across all scenarios, s-LPD improved survival (up to +0.59 life-years), increased QALYs (up to +0.48), and delayed dialysis initiation (up to +2.88 years) compared with LPD. From the NHS perspective, s-LPD was dominant in the optimistic scenario and cost-effective in both conservative and pessimistic scenarios, with cost savings or only a marginal cost that increases under extreme assumptions. Probabilistic sensitivity analyses confirmed a high probability of cost-effectiveness across scenarios. Results remained robust in additional scenario analyses, including the societal perspective. Conclusions: This first Italian cost-utility analysis of s-LPD highlights that s-LPD is a cost-effective strategy for patients with advanced CKD, offering clinically meaningful benefits while reducing or containing healthcare costs. These findings support the adoption of s-LPD as part of conservative management strategies aimed at safely delaying dialysis initiation.