Recent data reiterate low-protein diets (LPDs) as cornerstones in the conservative management of chronic kidney disease (CKD). The reduction in proteinuria, better blood pressure control and the reduction in the rate of decline in kidney function with LPDs were reported, both in non-diabetics and diabetics patients. Supplemented, vegetarian, very-low-protein diets (sVLPD, 0.3 g/kg-day) could postpone kidney replacement therapy (KRT) initiation, mainly through the better control of metabolic disorders of advanced CKD in non-diabetic patients. Plant-based diets could ameliorate gut microbiota and appear to be superior to mixed hypoproteic diets in treating advanced CKD: better control of nitrogen balance, acid-base metabolism and bone mineral disorders. Vegetarian diets generate fewer uremic toxins and reduce salt intake and acid overload. At the same time, they can improve lipid metabolism, providing a high ratio of unsaturated to saturated fatty acids, as well as insulin resistance.
Background and Aims Low-protein diets seem to have an important role in the management of advanced chronic kidney disease (CKD). In addition, this type of nutritional regimen may defer kidney replacement therapy by improving metabolic abnormalities. However, low-protein diets (LPDs) may be more difficult to integrate in patients with diabetic kidney disease (DKD), because of the already complex dietary intervention in these patients. This is a comparative study that aimed to assess the effects of a ketoanalogue-supplemented low-protein diet (sLPD) versus a conventional diet on the progression of CKD and proteinuria in patients with advanced DKD. Method Ninety-seven adult patients with DKD and heavy proteinuria (>3g/g creatininuria) who proved to be compliant to protein restriction in a 3-month run-in phase were enrolled to receive a LPD (0.6g 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 preemptive kidney transplant). The control group was made up of seventy-four adult patients with DKD and heavy proteinuria who received a conventional diet for 12 months. Efficacy outcomes were variation of the estimated glomerular filtration (eGF) and variation of proteinuria. Results At baseline, patients from the sLPD group had a median age of 61 years (95% CI 58 to 67), were mostly male (66%) and predominantly on insulin (68%). Patients in the control group had a median age of 60 years (95% CI 56 to 61), 62% were male and, similarly, the majority were on insulin (62%). All patients had poorly controlled diabetes, with a glycated hemoglobin of 8.1% (95% CI 8.0 to 8.3) in the sLPD group and 8.2% (95% CI 7.9 to 8.6) in the conventional-diet group respectively (P = .84). Although the median eGF was different between groups: 24.78 mL/min (95% CI 20.00 to 30.00) in sLPD patients versus 12.61 mL/min (95% CI 11.70 to 13.11) in conventional diet patients (p<0.0001), proteinuria was similar at baseline: 5.26 g/g creatininuria (95% CI 4.98 to 5.22) in sLPD patients and 4.05 g/g creatininuria (95% CI 3.70 to 5.80) in control group patients (P = .44). After 12 months, the decline of eFG (mL/min/month) was four-times slower in the sLPD group versus the control group [0.11 (95% CI 0.1 to 0.14) versus 0.43 (95% CI 0.30 to 0.57), p<0.0001]. A twofold reduction in proteinuria (g/month) was observed in sLPD patients compared to conventional diet patients [0.29 (95% CI 0.28 to 0.32) versus 0.12 (95% CI 0.09 to 0.15), p<0.0001]. Conclusion Low-protein diets supplemented with ketoanalogues of essential amino acids seem to be more efficient in reducing kidney function decline and proteinuria than conventional diets.
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.
Background and Aims Recent data suggest the possibility to optimize blood pressure control by low protein diet (LPD) in patients with diabetic kidney disease (DKD). We aimed to assess the effects of a low protein diet (LPD) supplemented with keto-analogues on urinary sodium excretion and blood pressure control. Method Prospective, uni-center study with a total duration of 15 months.The study was conducted in a tertiary Nephrology Clinic and included a total of 92 diabetic patients with advanced CKD (eGFR < 30 mL/min) and heavy proteinuria (> 3 g/g creatininuria). Intervention consisted in a LPD (0.6 g/kg-day) supplemented with keto-analogues of essential amino acids with nutritional counselling and adjustment of antihypertensive therapy. The primary efficacy parameter was proteinuria during intervention as compared to pre-enrolment. Blood pressure (BP), urinary sodium excretion, eGFR and blood glucose control were secondary end-points. Results Mean arterial pressure (MAP) decreased from baseline (Bs) to end of study (EOS) with -11 (-17 to -7) mmHg despite a reduction with 22% of patients needing antihypertensive medication. Independent predictors of a lower than median MAP (90mmHg) were a lower protein intake (HR 0.00 (0.00; 0.04; p=0.002), treatment with furosemide (HR 1.06 [1.06; 3.85]; p=0.03) but not with angiotensin-aldosterone system inhibitors (RAASi) [HR 0.17 (0.17; 0.90); p=0.03)] and was not influenced by natriuresis. Natriuresis decreased from 130 (121-135) to 80 (71-86) mmol/day (p<0.0001). A lower than median natriuresis (100mmol/day) was directly related to proteinuria [HR 0.0003 (0.00; 0.004); p=<0.0001], eGFR [HR 0.0001 (0.00; 0.14); p=0.01] and to diuretic therapy [0.21 (0.05; 0.83); p=0.03] but not to protein intake. Cardiovascular events were observed in 20% of patients and their occurrence was related to a lower MAP [0.97 (0.95; 0.99}; p=0.001]. No renal adverse were noted and the diet was nutritionally safe. Conclusion A low protein diet supplemented with ketoanalogues of essential amino acids on top of anti-hypertensive therapy (mostly loop diuretics) allows for a good control of blood pressure, unrelated to natriuresis in heavy proteinuric patients with advanced DKD.
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.
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