Long-term prognosis of hypoproteic diet supplemented with ketoanalogues in patients with advanced diabetic kidney disease and severe proteinuria

Abstract Background and Aims Studies support the role of low-protein regimens in managing chronic kidney disease (CKD). In addition, some data emphasize the role of low-protein diets (LPDs) in postponing kidney replacement therapy (KRT) in patients with CKD, even in diabetic patients with heavy proteinuria. Although most results seem to be in favor of a LPD in CKD, even in patients with advanced diabetic kidney disease (DKD), there is insufficient data on long-term kidney and patient outcomes. This is a follow-up study aimed to determine the outcomes in kidney survival and patient survival in patients with DKD and severe proteinuria. Method The follow-up study included all patients with advanced DKD and severe proteinuria who previously participated in a twelve-month uni-centric prospective study looking to assess variations in kidney function and proteinuria. At baseline, 97 patients with DKD, with stable stage 4+ CKD and proteinuria of nephrotic-range, who proved adherent to protein restriction were enrolled and received LPD (0.6 g mixed protein/kg-day) supplemented with ketoanalogues of essential amino acids (Ketosteril®, Bad Homburg, Germany, 1 tb/10 kg dry ideal body weight per day) for 12 months. Ninety-two patients completed the study (5 patients received kidney transplant). The efficacy outcomes were assessed by the decline of kidney function and proteinuria. Safety parameters were evaluated by anthropometric measurements (Body Mass Index), Subjective Global Assessment score and serum albumin. Compliance to the LPD was assessed by urinary urea from a 24-hour urine collection to estimate protein intake (ePI) and a 3-day food diary to estimate the energy intake. After the end of the study, the patients continued to remain compliant to the nutritional intervention. The primary composite endpoint was the need for KRT or patient death. The census moment was either the occurrence of the primary endpoint or the 31st of January, 2023. Results At baseline, patients had a median age of 61 years (95% CI 58 to 67), 66% were men, with poorly controlled diabetes assessed by the level of the glycated hemoglobin [8.1% (95% CI 8.0 to 8.3)]. All patients had a good nutritional status (SGA A). The median estimated glomerular filtration rate (eGF) was 12.6 mL/min (95% CI 11.7 to 13.1) and the median proteinuria was 5.2 g/g creatininuria (95% CI 5.0 to 5.2). After 12 months, a significant reduction in proteinuria was observed (67%), as well as a reduction in the kidney function decline by almost 80% compared to the period before the inclusion and a preserved good nutritional status (SGA A). The median follow-up was 105 months (95% CI 103 to 106). After almost 9 years of follow-up, 83.7% of patients remained alive, despite significant comorbidities. The median survival was 62 months (95% CI 47 to 85). Seventy-six percent of patients required KRT, with a predilection for hemodialysis. The median period of time until KRT was 26 months (95% CI 24 to 29). In a Kaplan-Meier survival analysis, the compliance to the sLPD was associated with better kidney survival (p = 0.03). Conclusion Low-protein diets supplemented with ketoanalogues of essential amino acids seem to be associated with a better kidney outcome on long-term in patients with advanced diabetic kidney disease and heavy proteinuria.