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.