Longitudinal Nutritional and Cardiorenal Changes Among Patients Prescribed a Ketoanalogue-Supplemented Very-Low-Protein Diet in Advanced Nondialysis Chronic Kidney Disease with Chronic Heart Failure: A Retrospective Cohort Study

Background/Objectives: Ketoanalogue-supplemented very-low-protein diets may reduce metabolic and mineral burden in advanced chronic kidney disease (CKD), but nutritional changes and adherence remain concerns. This study evaluated nutritional, renal, mineral–bone, hematologic, and cardiovascular changes in patients with advanced nondialysis CKD and chronic heart failure receiving this dietary regimen. Methods: This single-center retrospective cohort included 75 adults followed for 181–730 days, with a median follow-up of 243 days (interquartile range [IQR], 212–365 days). Prescribed protein and energy targets were 0.28–0.40 g protein/kg/day and 28–34 kcal/kg/day, respectively, with approximately one ketoanalogue tablet per 5 kg body weight/day and dietitian involvement. Paired analyses and exact-date body-weight sensitivity analyses were performed. Clinician-recorded adherence was summarized descriptively because assessment methods were not standardized. Results: The prespecified primary outcome, percentage body-weight change, had a Hodges–Lehmann estimate of −3.99% (95% CI, −4.68 to −3.42; p < 0.001). Mean body weight decreased from 75.85 ± 7.98 to 72.65 ± 7.09 kg, with a Hodges–Lehmann estimate of −3.10 kg (95% confidence interval [CI], −3.60 to −2.65; p < 0.001). Body mass index (BMI) also declined (estimate, −0.95 kg/m2; p < 0.001). A body-weight reduction of ≥5% occurred in 22 patients (29.3%); none had a reduction of ≥10%. The decrease remained evident among 62 patients followed for 181–366 days. Serum albumin and total protein increased slightly, while chart-recorded signs suggestive of nutritional deterioration were present in 25 patients (33.3%). Absolute eGFR change was modest (Hodges–Lehmann estimate, −1.50 mL/min/1.73 m2; 95% CI, −2.50 to −0.50; p = 0.007). Phosphorus, calcium–phosphorus product, intact parathyroid hormone, and alkaline phosphatase decreased, while calcium increased. Blood pressure showed little change, NYHA functional class was unchanged in 61 patients (81.3%), and left ventricular ejection fraction (LVEF) declined slightly. No maintenance dialysis initiation or death was documented before the final assessment. Conclusions: Body weight and BMI declined despite small cohort-level increases in serum proteins. Multidimensional nutritional monitoring and interpretation of weight change alongside fluid status are warranted. The absence of a control group, variable follow-up, and nonstandardized adherence assessment preclude causal interpretation.