Ketoanalogues Of Essential Amino Acids Research Articles

Low-Protein Diets Could Be Effective and Safe in Elderly Patients with Advanced Diabetic Kidney Disease.

Low-protein diets (LPDs) seem to improve metabolic complications of advanced CKD, thus postponing kidney replacement therapy (KRT) initiation. However, the nutritional safety of LPDs remains debatable in patients with diabetic kidney disease (DKD), especially in the elderly. This is a sub-analysis of a prospective unicentric interventional study which assessed the effects of LPD in patients with advanced DKD, focusing on the feasibility and safety of LPD in elderly patients. Ninety-two patients with DKD and stable CKD stage 4+, proteinuria >3 g/g creatininuria, good nutritional status, with confirmed compliance to protein restriction, were enrolled and received LPD (0.6 g mixed proteins/kg-day) supplemented with ketoanalogues of essential amino acids for 12 months. Of the total group, 42% were elderly with a median eGFR 12.6 mL/min and a median proteinuria 5.14 g/g creatininuria. In elderly patients, proteinuria decreased by 70% compared to baseline. The rate of kidney function decline was 0.1 versus 0.5 mL/min-month before enrolment. Vascular events occurred in 15% of cases, not related to nutritional intervention, but to the severity of CKD and higher MAP. LPDs seem to be safe and effective in postponing KRT in elderly patients with advanced DKD while preserving the nutritional status.

Low Protein Diet Reduces Proteinuria and Decline in Glomerular Filtration Rate in Advanced, Heavy Proteinuric Diabetic Kidney Disease.

Low protein diet (LPD) seems beneficial in ameliorating the complications of chronic kidney disease (CKD), in reducing proteinuria and the decline in kidney function, thus postponing the need for kidney replacement therapy (KRT). However, this type of intervention was less investigated in diabetic kidney disease (DKD). This is a single-center, prospective, interventional study that aims to assess the efficacy of reducing proteinuria and the rate of decline in the estimated glomerular filtration rate (eGFR). Patients with advanced DKD (stable proteinuria > 3 g/g and eGFR < 30 mL/min) with a good nutritional status and accepting a LPD were evaluated for inclusion. Ninety-two of the 452 screened patients (66% males, median age 61 years, proteinuria 4.8 g/g creatininuria, eGFR 11.7 mL/min/1.73 m2) completed the study. Intervention consisted of LPD supplemented with ketoanalogues of essential amino acids (KA) along with conventional nephroprotective therapy. Efficacy parameters were the variation in proteinuria and in eGFR from baseline to the end of the study. Proteinuria decreased 3-fold, and the rate of decline in eGFR decreased 5-fold in the intervention phase. No patient initiated KRT or died. LPD supplemented with KA seems effective in safely postponing KRT by reducing proteinuria and the decline in kidney function in advanced DKD.

EE115 Cost-Effectiveness Analysis of Using Ketoanalogues of Essential Aminoacids in Patients With Chronic Kidney Disease in Kazakhstan

EE115 Cost-Effectiveness Analysis of Using Ketoanalogues of Essential Aminoacids in Patients With Chronic Kidney Disease in Kazakhstan

Economic Analysis of a Ketoanalogue-supplemented Very Low-protein Diet in Patients With Chronic Kidney Disease in Vietnam

The aim of this study was to estimate the cost-effectiveness of a very low-protein diet (VLPD) supplemented with ketoanalogues of essential amino acids compared with a conventional low-protein diet (LPD) in Vietnam. The study was conducted from payer (base case), patient, and societal perspectives. A Markov model simulated costs and quality-adjusted life-years (QALYs) for patients with chronic kidney disease stage 4 or 5 (CKD4+) who were followed up during their lifetimes. Patients received a VLPD (0.3- to 0.4-g/kg/d diet) supplemented with ketoanalogues (5 kg/d [1tablet]) versus LPD (0.6 g/kg/d, mixed proteins). In each model cycle, patient transitions among the health states-CKD4+ (nondialysis), dialysis, and death-were based on transition probabilities taken from the published literature. The time horizon covered the cohort's lifetime. Utilities and costs were estimated from literature review and projected for the lifespan considered in the model. Probabilistic and deterministic sensitivity analyses were performed. The ketoanalogue-supplemented VLPD increased survival and QALYs compared with the LPD. From a payer's perspective, total cost of care in Vietnam was ₫216,854,268 (€8684/$9242) per patient with LPD versus ₫200,928,819 (€8046/$8563) per patient with a supplemented VLPD (sVLPD) (difference, -₫15,925,449 [-€638/-$679]). From a patient's perspective, total cost of care in Vietnam was ₫217,872,043 (€8724/$9285) per patient with LPD versus ₫116,015,672 (€4646/$4944) per patient with sVLPD (difference, -₫101,856,371 [-€4,079/ -$4341]). From a societal perspective, total cost of care in Vietnam was ₫434,726,312 (€17,408/-$18,527) per patient with LPD versus ₫316,944,491 (€12,692/ $13,508) per patient with sVLPD (difference, -₫117,781,820 [-€4716 €/$5020). Ketoanalogue-supplemented VLPD lowered costs compared with LPD in all 3 perspectives considered.

#6423 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.

#6375 HYPOPROTEIC DIET SUPPLEMENTED WITH KETOANALOGUES VERSUS CONVENTIONAL DIET IN PATIENTS WITH ADVANCED DIABETIC KIDNEY DISEASE AND SEVERE PROTEINURIA

Abstract 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 (&amp;gt;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&amp;lt;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&amp;lt;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&amp;lt;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.

Myocardial effects of a low-protein diet in experimental kidney dysfunction

THE AIM: to evaluate the effect of low protein diet supplemented with ketosteril on morphological and epigenomic changes in the myocardium of Wistar rats with simulated kidney dysfunction . MATERIALS AND METHODS. The work was performed on male Wistar rats subjected to 5/6 nephrectomy (NE). The first group after NE received a standard diet (20.16% animal protein ), the second – low protein diet (LPD), including 10% ketosteril . Control rats received a standard diet . After 4 months , blood pressure (BP) and left ventricular mass index (LVMI) were assessed in rats , and a histological examination of the myocardium was performed . In the myocardium , the relative expression levels of NF- kB , miRNA-21, miRNA-133, and miRNA-203 were determined . RESULTS. After 4 months in rats with NE on a standard diet , an increase in blood pressure , an increase in the mass index of the LV myocardium was recorded . MBD with the inclusion of 10% Ketosteril slowed down the growth of systolic blood pressure and the development of LV myocardial hypertrophy in rats with kidney dysfunction . At the histological level , the use of LPD provided a decrease in the degree of hypertrophy of cardiomyocytes and degenerative changes in cardiomyocytes . Animals treated with LPD had less pronounced diffuse and perivascular fibrosis compared with animals fed normal food . The use of MBD slowed down the increase in the relative level of expression of the NFκB gene and miRNA-21 in the myocardium of rats with NE and promoted an increase in the expression level of miRNA-133 and miRNA-203 compared to the indices of animals with NE that received standard food . CONCLUSION: long-term use of LPD with the use of ketoanalogues of essential amino acids can have a potential cardioprotective effect in CKD, slowing down the growth of blood pressure , an increase in LV myocardial mass and the formation of structural changes in the myocardium . It is possible that a decrease in the expression of NF- kB and miRNA-21, as well as an increase in the expression of miRNA-203 and 133 in the myocardium , can play a significant role in this .

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 (&amp;gt;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 &amp;lt; 0.0001, Negelkerke R Square test 58%, Hosmer &amp; 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.

POS-262 LOW-PROTEIN DIETS IN CHRONIC KIDNEY DISEASE – SAFE OR NOT? A SINGLE LARGE CENTER EXPERIENCE

Recent studies emphasized the role of low-protein diets (LPDs) in the management of chronic kidney disease (CKD) in order to postpone renal replacement therapy. However, the risk of malnutrition in CKD patients on LPDs has often been debated. We present the results of a large single-center, focusing on the safety of LPDs in both diabetic and non-diabetic patients with CKD. A prospective, randomized, controlled study with 207 non-diabetic patients with CKD stage 4+ were grouped by the type of nutritional intervention - vegetarian very low protein diet with 0.3g/kg-day supplemented with ketoanalogues of essential aminoacids (sVLPD) versus LPD with 0.6g/kg-day for 15 months. We present the safety parameters at the end of study (EOS), but also after 10 years of follow-up. Safety data from a second interventional study, including 97 diabetic patients with stage 4+ CKD who received LPD supplemented with ketoanalogues of essential aminoacids (sLPD) for 12 months are also presented. Subjective Global Assessment (SGA), clinical data (Body Mass Index, BMI), and biochemical parameters (serum albumin, C-reactive protein) were analyzed. Patients’ adherence to the type of nutritional intervention was assessed by the estimated protein intake using urinary urea excretion. Both protein and energy intake were also evaluated through food diary. Nutritional status of non-diabetic patients was preserved for both sVLPD and LPD at 15 months after inclusion (SGA A 84 versus 85%, p=0.83). Moreover, the subjects continued the nutritional intervention after the EOS. After 10 years of nutritional intervention, the kidney’s survival (86 versus 46%, p<0.0001) and patients’ survival (89 versus 60%, p<0.0001) were much better in the sVLPD group. The levels of serum albumin were constantly around 4 g/dL, without any significant differences between groups at all study moments. The C-reactive protein levels were lower in patients on sVLPD at 15 months after inclusion (4 versus 5 mg/L, p<0.0001), respectively at 10 years after inclusion (5 versus 10 mg/L, p<0.0001). Patients’ adherence was confirmed at all study moments. For diabetic patients, during the study, there were improvements in body weight (BMI 27.1 versus 26.0 kg/m², p<0.0001), serum albumin (3.9 to 4.1 g/dL, p<0.0001), and in C-reactive protein levels (14 to 9 mg/L, p<0.0001). All patients had SGA A throughout the study. Nutritional intervention with different low-protein regimens seem to be safe for patients with CKD, both in diabetics and in non-diabetics.

The value of a low-protein diet and ketoanalogues of essential amino acids in the сontrol of protein carbamylation and toxic effects of urea in chronic kidney disease

Chronic kidney disease (CKD) is characterized by high mortality from cardiovascular diseases, the development of which is facilitated by traditional risk factors (typical for the general population) and by nontraditional ones (specific to patients with CKD) as well. These factors include also uremic toxins, for which a causal relationship has been established with specific pathological processes in patients with CKD, comprising the development of vascular dysfunction and accelerated progression of atherosclerosis. Urea has long been considered not as a uremic toxin, but as a marker of metabolic imbalance or dialysis efficiency (Kt/V) in CKD patients. In recent years, more and more publications have appeared on the study of the toxic effects of urea with the development of toxic-uremic complications and the phenotype of premature aging, common in CKD. It was found that an increase in urea levels in uremic syndrome causes damage to the intestinal epithelial barrier with translocation of bacterial toxins into the bloodstream and the development of systemic inflammation, provokes apoptosis of vascular smooth muscle cells, as well as endothelial dysfunction, which directly contributes to the development of cardiovascular complications. The indirect effects of increased urea levels are associated with carbamylation reactions, when isocyanic acid (a product of urea catabolism) changes the structure and function of proteins in the body. Carbamylation of proteins in CKD patients is associated with the development of renal fibrosis, atherosclerosis and anemia. Thus, urea is now regarded as an important negative agent in the pathogenesis of complications in CKD. Studies on a low-protein diet with using ketoanalogues of essential amino acids to minimize the accumulation of urea and other uremic toxins demonstrate the clinical benefit of such an intervention in slowing the progression of CKD and the development of cardiovascular complications.

Nutritional support for patients with chronic kidney disease at pre-dialysis stages

Chronic kidney disease (CKD) is characterized by poor outcomes, an increasing frequency of new cases, the need for expensive method of renal replacement therapy at the terminal stage. The main task facing the doctor is slowing the progression of CKD and delay the start of dialysis by applying the nephroprotective strategy, of which diet therapy is an essential part. The key components of the diet for CKD patients are reducing sodium intake to 2.3 g per day in order to improve control of blood pressure (BP), dietary protein restriction adequate to renal function from 0.8 to 0.3 g/kg of body weight per day combined with the prescribing of ketoanalogues of essential amino acids, hyperglycemia control. With the progression of CKD, the main objectives of the diet therapy are the prevention/correction of complications: protein-energy waisting, metabolic acidosis, ensuring sufficient calories, corresponding to the bodys energy expenditures (3035 kcal/kg of body weight per day), limiting phosphate intake to 0.81 g a day, restriction of food potassium. Low-protein diet in combination with ketoanalogues of amino acids, regular monitoring and correction of the nutritional status of patients at the pre-dialysis stages of CKD is an effective and safe method of nephroprotection, which allows delaying the start of dialysis.

P0929LOW PROTEIN DIET, BLOOD PRESSURE CONTROL AND NATRIURESIS IN PATIENTS WITH ADVANCED DIABETIC KIDNEY DISEASE AND HEAVY PROTEINURIA

Abstract 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 &amp;lt; 30 mL/min) and heavy proteinuria (&amp;gt; 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&amp;lt;0.0001). A lower than median natriuresis (100mmol/day) was directly related to proteinuria [HR 0.0003 (0.00; 0.004); p=&amp;lt;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.

Современные принципы нефропрофилактики и ренопротективные эффекты малобелковой диеты с применением кетоаналогов незаменимых аминокислот у пациентов с хронической болезнью почек

Статья посвящена одной из наиболее актуальных проблем в нефрологии — хронической болезни почек. Дана характеристика факторов риска развития этой патологии, а также основных направлений ее лечения. Подчеркнута немаловажная роль коррекции питания в комплексе лечения хронической болезни почек. Патогенетически обоснованным является применение малобелковой диеты с включением кетоаналогов аминокислот (Кетостерила), что обеспечивает ренопротективное действие, дает возможность увеличить додиализный период и способствует улучшению качества жизни больных с хронической болезнью почек.

Ренопротективные эффекты малобелковой диеты с применением кетоаналогов незаменимых аминокислот

В статье рассматривается роль малобелковой диеты и кетоаналогов незаменимых аминокислот у больных с нарушением функции почек. По результатам исследования закономерности формирования уровня моноцитарного хемоаттрактантного протеина (МСР-1), в зависимости от генеза гломерулярных повреждений и стадии хронической болезни почек, и его динамики под воздействием различных подходов в комплексном лечении сделан вывод, что назначение малобелковой диеты с включением Кетостерила необходимо уже на ранних стадиях заболевания с целью ренопротективного действия. Применение Кетостерила должно быть длительным и постоянным с целью увеличения додиализного периода и улучшения качества жизни больных с хронической болезнью почек.

Long-term effects of a new ketoacid–amino acid supplement in patients with chronic renal failure

Nine patients with severe chronic renal failure (mean glomerular filtration rate 4.8 ml/min; mean serum creatinine 11.3 mg/dl) who were previously on a protein-restricted diet were treated with a diet containing an average of 33 kcal/kg and 22.5 g/day of mixed quality protein, supplemented by a combination of amino acids and mixed salts formed between basic amino acids and keto-analogues of essential amino acids. The supplement was designed to minimize or reverse the amino acid abnormalities of chronic renal failure rather than to meet the normal requirements for the essential amino acids; it contained tyrosine, ornithine, and a high proportion of branched-chain ketoacids, but no phenylalanine or tryptophan and very little methionine. Within one month, serum urea nitrogen fell and serum albumin and transferrin rose significantly; serum creatinine fell slightly. Hyperphosphatemia (present in three patients) was corrected. Nitrogen balance, measured in seven of the nine patients, on the average was neutral, as it was in a preceding control period on a 40 to 50 g/day protein diet. Plasma tyrosine and threonine, which were subnormal before therapy, rose to normal or high normal levels. Branched-chain amino acids did not change. During a total of 63 patient-months of therapy, no side effects or toxicity were observed, and serum albumin and transferrin did not change further. It is concluded that this specially designed supplement added to a 20 to 25 g/d protein diet is an acceptable regimen which can improve or maintain protein nutrition in patients with severe chronic renal failure who would otherwise require dialysis.

Absorption of Keto-Analogues of Branched-Chain Amino Acids from Rat Small Intestine

The keto-analogues of essential amino acids provide a source of essential amino acids that contain no nitrogen, but little is known about the mechanism of keto-analogue intestinal absorption. Absorption of the keto-analogue of valine was compared with that of the corresponding amino acid valine by perfusing rat jejunum and ileum in vivo. In both ileum and jejunum, keto-valine was absorbed at rates only moderately below those of the amino acid valine when perfused at 1–50 mM. In the jejunum, absorption rates for keto-valine relative to valine ranged from 73% to 39% at perfusate concentrations of 1 mM and 25 mM, respectively. Similar results were obtained in the ileum. The absorption curve of keto-valine was nonlinear at low perfusate concentrations and linear at higher concentrations, consistent with both saturable transport and passive diffusion. In further studies, 3 mM keto-valine was perfused into jejunal segments. Twenty-five millimolar of the keto-analogues of isoleucine and phenylalanine inhibited keto-valine absorption by 43% and 50%, respectively, whereas 3 mM of the keto analogue of isoleucine did not. Sixty-seven millimolar valine and 56 mM glucose significantly increased keto-valine absorption by 30% and 57% respectively; there were corresponding fourfold and eightfold increments in water transport. The keto analogues of leucine and isoleucine were absorbed at the same rates as keto-valine when perfused at 3 mM and 25 mM. Arterial and mesentric venous blood was sampled after perfusing 25 mM of keto-leucine and keto-isoleucine. There was a significant release of the corresponding amino acids into mesentric venous blood compared with controls, which suggest partial transamination during absorption. The data indicate: (a) Keto-analogues of the branched-chain amino acids are absorbed at rates moderately below those of the corresponding amino acids; (b) keto-valine absorption is in part mediated throught a saturable mechanism; (c) keto-valine absorption is influenced by solvent drag; and (d) partial transamination occurs during keto-analogue absorption in the rat jejunum.

The effect of keto-analogues of essential amino acids in severe chronic uremia.

Alpha keto-analogues of valine, leucine, isoleucine, methionine, phenylalanine, and (in one instance) tryptophan and histidine, along with the remaining essential amino acids, were administered orally to 10 patients with severe chronic uremia fed a diet low in protein but adequate in calories. Ketoacid dosage varied from 6 to 14 g daily, as sodium or calcium salts. Net nitrogen intake, calculated as intake minus urinary protein nitrogen, averaged 1.8 g/day. The urea space was either estimated or measured with [(14)C]urea and daily changes in the body urea pool were calculated. Urea appearance was measured as the sum of urea excretion and the change in urea pool. If these ketoacids were converted to amino acids and utilized for protein synthesis, a fall in urea nitrogen appearance should occur. In five subjects, ketoacids were given for 15-18 days and then withdrawn. Urea nitrogen appearance increased 1.55 g/day on withdrawing ketoacids, and corrected nitrogen balance decreased by 1.73 g/day. In two other subjects ketoacid administration was followed, on two occasions each, by a period of administration of nine essential amino acids. In three of these four instances, urea appearance rose significantly with amino acids. In four patients studied at high blood urea levels, ketoacid treatment was relatively ineffective; two of these patients responded more favorably when studied again after peritoneal dialysis. One of these improved enough clinically to be managed as an out-patient for short intervals, despite virtual anuria. No accumulation of ketoacids in plasma or urine could be detected, and no toxicity was identified.