MO586: Low-Protein Diet Supplemented With Ketoanalogues of Essential Amino Acids in Advanced Diabetic Kidney Disease: Safety Issues in Elderly

Abstract

BACKGROUND AND AIMS Lately, studies support the role of dietary protein restriction in the management of patients with chronic kidney disease (CKD). Beneficial effects were noticed in ameliorating metabolic disturbances in advanced CKD and optimizing the blood pressure control, thus postponing kidney replacement therapy. However, nutritional safety of low-protein diets (LPDs) remains debatable, especially in elderly. This prospective unicenter interventional study aimed to assess the effects of LPD in advanced diabetic kidney disease (DKD). We present a sub-analysis of data focusing on the safety in elderly patients. METHOD Ninety-two patients with DKD with stable CKD stage 4+, heavy proteinuria (>3 g/g creatininuria), good nutritional status (Subjective Global Assessment—SGA A) and compliant to protein restriction proved during a 3-month run-in phase (21% of the screened population) were enrolled and received conventional 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 (sLPD) for 12 months. Efficacy outcomes were the variation of proteinuria (primary outcome) and the variation of estimated glomerular filtration rate, eGFR (secondary outcome). Safety was assessed throughout the study using anthropometric measures (Body Mass Index, BMI), SGA, serum albumin (SAlb). Inflammatory parameters (C-reactive protein, CRP) and the occurrence of adverse reactions were also recorded. Compliance was evaluated using urinary urea from 24-h urine collection to estimate the protein intake (ePI) and the 3-day food diary for energy intake (EnI). RESULTS Ninety-two patients [61% males, median age 61 (58–67) years, eGFR 11.7 (11.2–12.2) mL/min/1.73 m², proteinuria 4.8 (4.6–5.2) g/g creatininuria] completed the study. For the whole group, proteinuria decreased with 67% from the baseline to the end of study (EOS), and the rate of decline in eGFR was reduced with 80% compared with the period before enrolment. Of the total group, 42% (39 patients) were elderly (≥65 years): median age 75 (71–80) years old, 64% males, median eGFR 12.61 (11.16–13.81) mL/min and median proteinuria 5.14 (4.84–5.25) g/g creatininuria. About 21% (19 patients) were late elderly (≥75 years old). In elderly, proteinuria significantly decreased: 1.51 (0.98–1.75) versus 5.14 (4.84–5.26) g/g creatininuria, i.e. by 70% of the baseline value. eGFR also significantly decreased: 10.73 (9.87–11.68) versus 12.61 (11.16–13.81) mL/min. To note, the rate of decline in kidney function was 0.1 versus 0.5 mL/min-month before enrolment, i.e. 5 times slower. The nutritional status was improved: BMI decreased [25.58 (24.68–26.98) versus 27.08 (25.47–28.11) kg/m² at baseline] and the percentage of overweighted subjects declined (56.4 versus 76.9%), while SGA did not change during the study. SAlb was also stable: 4.19 (4.03–4.30) versus 3.90 (3.86–3.99) mg/dL. The inflammatory status was significantly ameliorated: CRP decreased, 8 (7–9) versus 14 (12–15) at baseline mg/L. Thus, by the EOS the percentage of patients with inflammation (CRP ≥ 10 mg/L) significantly decreased: 23.1 versus 92.3% at baseline. The ePI and EnI were very close to recommendations and remained stable during the study: 0.64 (0.63–0.67) versus 0.68 (0.65–0.69) g/kg-day for ePI and 31.30 (28.50–33.00) versus 31.16 (30.16–32.56) kcal/kg-day for EnI at EOS versus baseline, respectively. In a binary regression analysis, lower levels of CRP were associated with sLPD, lower proteinuria and higher SAlb (P < 0.0001, Negelkerke R Square test 58%, Hosmer & Lemeshow test 0.11). No adverse reactions were noted. CONCLUSION In elderly patients with advanced DKD, low protein diet supplemented with ketoanalogues of essential amino acids seems to be effective in reducing the decline in eGFR and proteinuria, while being also nutritionally safe.