No additional benefit of prescribing a very low-protein diet in patients with advanced Chronic Kidney Disease under regular nephrology care: a pragmatic, randomized, controlled trial

Background: Whether very low-protein diet supplemented with ketoanalogs (sVLPD), compared to standard low-protein diet (LPD), improves outcomes in chronic kidney disease (CKD) patients under stable nephrology care is undefined. Objective: To compare the effectiveness of sVLPD vs LPD in patients regularly seen in tertiary nephrology care. Methods: Participants were CKD patients stage 4-5, followed for at least six months, randomized to receive sVLPD or LPD (0.35 or 0.60 g/kg Ideal Body Weight (IBW)/day, respectively), stratified by center and CKD stage. The primary outcome was time to renal death, defined as the first event between end-stage renal disease (ESRD) and all-cause mortality; secondary outcomes were the single components of the primary outcome, cardiovascular outcome, and nutritional status. Results: We analysed 223 patients (sVLPD n = 107; LPD n = 116). Mean age was 64 years, 61% were male, 35% had diabetes. Median protein intake (PI), that was 0.8 g/kg IBW/day at baseline in both groups, was 0.83 and 0.60 g/kg IBW/day in LPD and sVLPD, respectively, during the trial with a large decrease only in sVLPD (P = 0.011). During a median of 74.2 months, we recorded 180 renal deaths (141 dialysis and 39 deaths before dialysis). Risk of renal death did not differ in sVLPD vs LPD (HR 1.17, 95%CI 0.88,1.57, P = 0.28). No difference was observed for ESRD (HR 1.12, 95% CI 0.81,1.56, P = 0.51), mortality (HR 0.95, 95%CI 0.62,1.45, P = 0.82) or time to fatal/non-fatal cardiovascular events (P-value log-rank test = 0.2). After 36 months, still active patients were 45 in sVLPD and 56 in LPD. No change of nutritional status emerged during the study in any arm. Conclusions: This long-term pragmatic trial found that in CKD patients under stable nephrology care, adherence to protein restriction is low. Prescribing sVLPD versus standard LPD was safe but does not provide additional advantage to the kidney or patient survival