P0929LOW PROTEIN DIET, BLOOD PRESSURE CONTROL AND NATRIURESIS 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.

Keto analogues and amino acid supplementation and its effects on ammonaemia during extenuating endurance exercise in ketogenic diet-fed rats

Keto analogues and amino acids (KAAA) supplementation can reduce blood ammonia concentrations in athletes undergoing high-intensity exercise under both ketogenic and thermoneutral conditions. This study evaluated the acute effects of KAAA supplementation on ammonia metabolism during extenuating endurance exercise in rats fed a ketogenic diet. In all, eighty male Fischer rats at 90 d of age were divided into eight groups, and some were trained using a swimming endurance protocol. A ketogenic diet supplemented with keto analogues was administered for 10 d. Administration of the ketogenic diet ended 3 d before the exhaustion test (extenuating endurance exercise). A ketogenic diet plus KAAA supplementation and extenuating endurance exercise (trained ketogenic diet supplemented with KAAA (TKKa)) increased blood ammonia concentrations by approximately 50 % compared with the control diet (trained control diet supplemented with KAAA (TCKa)) and similar training (effect size=1·33; statistical power=0·50). The KAAA supplementation reduced blood urea concentrations by 4 and 18 % in the control and ketogenic diet groups, respectively, compared with the groups fed the same diets without supplementation. The trained groups had 60 % lower blood urate concentrations after TCKa treatment than after TKKa treatment. Our results suggest that KAAA supplementation can reduce blood ammonia concentrations after extenuating endurance exercise in rats fed a balanced diet but not in rats fed a ketogenic diet.

Efficiency of post-dilution online hemodiafiltration therapy in combination with ketoanalogues of amino acid in the correction of protein-energy malnutrition in hemodialysis patients

Purpose of the study. Evaluate the efficiency of permanent post-dilution online hemodiafiltration therapy in combination with the prescription of keto analogues of amino acid at a dose of 0,2 g/kg of ideal body weight/day to correct protein-energy malnutrition in hemodialysis patients with adequate intake of essential nutrients. Patients and methods. A total of 645 patients with terminal renal failure received programmed hemodialysis, of which there were 300 men and 345 women aged 58,8 ± 6,9 years. All patients received treatment with programmed GD for 6,9 ± 2,1 years. All patients underwent a comprehensive assessment of nutritional status. The level of leptin and interleukin-6 serum was determined. Patients with signs of protein-energy malnutritian (PEM) were divided into three groups, depending on the method of PEM correction. Results. The study showed the efficiency of postdilution online hemodiafiltration therapy on an ongoing basis in combination with keto-analogues of amino acids at a dose of 0,2 g/kg of ideal body weight/day for correction of PEM in hemodialysis patients. Conclusion. The post-dilution online hemodiafiltration therapy combined with keto-analogues of amino acid at a dose of 0.2 g /kg of ideal body weight/day can be considered one of the pathogenetically grounded methods for correcting PEM in patients receiving programmed hemodialysis with adequate intake of essential nutrients.

INTERNATIONAL SYMPOSIUM «KETO-ANALOGUES OF ESSENTIAL AMINO ACIDS»

.

Role of rhubarb and α-keto analogues of essential amino acids supplementation in halting progression of chronic kidney disease

Background: Chronic kidney disease (CKD) is an emerging chronic disease due to rapidly increasing incidence of diabetes and hypertension worldwide. Newer drugs are being searched which can stop nephron damage and are cost effective. This study was undertaken to compare the efficacy and safety profile of rhubarb and α-keto analogues of essential amino acids supplementation in patients of chronic kidney disease.Methods: A prospective comparative study was conducted in patients of chronic kidney disease attending Renal Clinic of a tertiary care centre. Randomization of patients was done into three interventional groups: conservative management along with placebo was given in first group (Control); conservative management along with Rhubarb capsule (350 mg, thrice daily) was given in second group (Rhubarb) and conservative management along with α-keto analogues of essential amino acids (600 mg, thrice daily) was given in third group (KAA). The treatment was given for 12 weeks. Clinical and biochemical parameters were assessed at 0, 4, 8 and 12 weeks of treatment.Results: Patients of all three groups showed gradual improvement in clinical features and biochemical parameters as compared to their pre-treated values which was more marked in KAA supplemented group. There was reduction in: fasting blood glucose (12.51%, 19.15% and 20.78%), PPBG (14.80%, 19.00% and 20.89%), serum creatinine (25.00%, 30.54% and 39.52%), blood urea (25.55%, 33.64% and 38.09%), and 24-hour total urine protein (TUP) (19.80%, 30.18% and 38.34%) in Group I, II and III respectively. There was increase in: haemoglobin level (12.64%, 14.99% and 19.77%), 24-hour total urine volume (TUV) (19.41%, 28.82% and 33.32%) and GFR (22.6%, 46.5% and 49.2%) in Group I, II and III respectively. Rhubarb and KAA supplementations were safe and well-tolerated.Conclusions: KAA is more effective than Rhubarb as add on therapy with conservative management in patients of chronic kidney disease.

Friedel–Crafts Chemistry. Part 48. Concise Synthesis of Condensed Azaheterocyclic [1,8]naphthyridinones, Azepino-, Azocino-, and Azoninoquinoline Systems via Friedel–Crafts Ring Closures

Unprecedented construction of a novel series of quinoline heteropolycycles (tetracyclic keto-analogues of [1,8]naphthyridinones, azepino-, azocino- and azonino[2,3-b]quinolinones systems) 10a–i by Friedel–Crafts cycliacylation reactions is described. Starting heterocyclic acids precursors 3a–i were prepared from easily accessible 2-chloroquinoline-3-carbaldehyde 1 via a three different synthetic pathways. Acid-catalyzed ring closures of the resulting tosylated acids were achieved under the influence of both Brønsted and Lewis acid catalysts. The present strategy enables a straightforward synthesis to fused tetracyclic quinolinone skeletons as demonstrated by concise and atom-economical syntheses.