BENEFICIAL EFFECT OF KETO AMINO ACIDS FOR DIALYSIS PATIENTS

Nutritional status is an important predictor of clinical outcome in dialysed patients. Beside decreased serum protein/albumin,lower BMI with decreased muscle mass is the most significant predictor of morbidity and mortality. Keto amino acids (KA) represent an additional source for protein anabolism influencing indirectly also carbohydrate and lipid metabolism,Ca-P and acid base balance.Additionaly,by concominant metabolic and hemodynamic effect on residual nefrons, KA can help to slow progression of residual renal function (RRF) mainly in peritoneal dialysis patients. We conducted a long-term prospective randomized placebo controlled trial to test whether a modified low-protein diet (LPD) with or without keto acids (KA) would be safe ,well tolerated and associated with an increase of metabolic status and preservation of RRF in peritoneal dialysis (PD). We evaluated a total of 62 PD patients (32M/30F) aged 26-72 yrs with creatinine clearance (Ccr) 7.9-5.7 mL/min/1.73m2 for a period of 12 months. All patients were on modified LPD containing 0.8 protein/kg/IBW/day and 135/kJ/kg/IBW/day. LPD was randomly supplemented with KA at dosage of 100 mg/kg/IBW/day (30 patients, Group I) while 30 patients (Group II) received placebo. We analysed also muscle and fat metabolism by MR spectroscopy (MRS, m.tibialis anterior)) and imagining (MRI,visceral fat).Patients from Group I were before enrolment on conservative management using LPD + KA (0.6g P + 0.1g KA/kg/IBW/day) for longer time (18-48 months, median 28) with good compliance (SGA). Patients from group II were never treated with LPD and KA.All patients were monitored at the beginning of PD and at every 3 months for 12 months.;A neutral or positive long- term nitrogen balance (nPCR in g/kg IBW/day) was achieved in Group I (p<0.05 ).RRF measured as Ccr remained stable in Group I (6.5 ± 2.18 to 5.9 ± 2.54 ml/min, p=NS),while it decreased in Group II (6.7 ± 2.22 to 3.2 ± 1.44 ml/min, p<0.02).There were no differences in Dialysate clearance (DCcr(L/week/1.73 m2).At the end of the study,there were significant differences in Total clearance per week expressed as Dialysate clearance + Residual creatinine clearance (TCcr=DCcr + RCcr), P< 0.01 and Total Kt/Vurea/week,P< 0.01.Serum albumin increased significantly (from 29.5 ± 2,5 to 35.4 ± 3.4 g/L, P< 0.01) in Group I comparing to Group II ( 30.4 ± 3.4 to 31.8 ± 3.5 g/L, P =ŃS).Also urine output was sigificantly higher in Group I (1226 ± 449 mL/day) than in Group II ( 678± 327 mL/day, P< 0.01), respectively).Fat in muscle measured by MR spectroscopy (MRS, m.tibialis anterior) significantly decreased in Group I and was linked to reduced volume of visceral fat measured by MRI (p<0.02). In conclusion, comparing to control Group II, long-term administration of modified LPD+KA was associated in Group I with better metabolic status and residual renal function.(RRF ,diuresis,Total clearance,Total Kt/V (urea),,.S-albumin and nPCR).We confirmed positive changes in muscle mass and fat metabolism measured by MRS and MRI. Long-term administration of KA supplemented diet in dialysed patients was safe and well tolerated.Thus,this regimen may ramarkable increase nutritional status and clinical outcome of dialysed patients

COSMOS: the dialysis scenario of CKD-MBD in Europe

Background Chronic kidney disease-mineral and bone disorders (CKD-MBD) are important complications of CKD5D patients that are associated with mortality. Methods COSMOS is a multicentre, open cohort, prospective, observational 3-year study carried out in haemodialysis patients from 20 European countries during 2005-07. The present article describes the main characteristics of the European dialysis population, the current practice for the prevention, diagnosis and treatment of secondary hyperparathyroidism and the differences across different European regions. Results The haemodialysis population in Europe is an aged population (mean age 64.8 ± 14.2 years) with a high prevalence of diabetes (29.5%) and cardiovascular disease (76.0%), and 28.7% of patients have been on haemodialysis more than 5 years. Patients from the former Eastern countries are younger (59.3 ± 14.3 versus 66.0 ± 13.9), having a lower proportion of diabetics (24.1 versus 30.7%). There were relevant differences in the frequency of measurement of the main CKD-MBD biochemical parameters [Ca, P and parathyroid hormone (PTH)] and the Eastern countries showed a poorer control of these biochemical parameters (K/DOQI and K/DIGO targets). Overall, 48.0% of the haemodialysis patients received active vitamin D treatment. Calcitriol use doubled that of alfacalcidiol in the Mediterranean countries, whereas the opposite was found in the non-Mediterranean countries. The criteria followed to perform parathyroidectomy were different across Europe. In the Mediterranean countries, the level of serum PTH considered to perform parathyroidectomy was higher than in non-Mediterranean countries; as a result, in the latter, more parathyroidectomies were performed in the year previous to inclusion to COSMOS. Conclusions The COSMOS baseline results show important differences across Europe in the management of CKD-MB

Muscle and Fat Metabolism in Obesity After Kidney Transplantation: No Effect of Peritoneal Dialysis or Hemodialysis

Our prospective study analyzed selected adipocytokines: adiponectin (ADPN), leptin, visfatin, and asymmetric dimethylarginine (ADMA) in the plasma of renal transplant recipients previously treated by peritoneal dialysis and hemodialysis. A total of 70 patients were on follow-up for 12 months after transplantation. Of these, 30 patients (group I) developed obesity, and 40 patients were nonobese (group II). All were receiving standard immunosuppressive therapy (cyclosporine A or tacrolimus and mycophenolate mofetil, with prednisone added in the early posttransplant period) and did not differ statistically in HLA typing, age, sex, duration of previous dialysis, history of cardiovascular disease, and rate of rejection episodes. At the end of the study period, there were significant differences between groups I and II (t test, analysis of variance) in plasma: ADPN, 22.30 +/- 10.2 versus 14.3 +/- 7.2 mu g/mL; visfatin, 1.7 +/- 0.1 versus 1.2 +/- 0.1 ng/mL; ADMA, 3.60 +/- 0.47 versus 2.10 +/- 0.36 mu mol/L; P < 01; leptin, 55.6 +/- 10.2 versus 25.6 +/- 8.3 ng/L; P < .01 (P < .02). In conclusion, an increase of body fat after renal transplantation was associated with an increase of ADMA and leptin, TNF-alpha, MCP-1, and visfatin and decrease of adiponectin. Our study documented there was now long-term beneficial metabolic effect of peritoneal dialysis in developing posttransplant obesity. (C) 2012 by the National Kidney Foundation, Inc. All rights reserved

Effect of keto amino acids on asymmetric dimethyl arginine, muscle and fat tissue in chronic kidney disease

Levels of endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) are elevated in chronic kidney disease (CKD) and may contribute to vascular complications. In this study we tested the hypothesis that elevated ADMA can be reduced in CKD patients by long-term administration of low-protein diet (LPD) supplemented with keto amino acids (KA). In a long-term prospective double blind placebo controlled randomized trial, we evaluated a total of 120 CKD patients (62/58F) aged 22-76 yrs with creatinine clearance 22-40mL/min/1.73m2 for a period of 36 months. All patients were on low-protein diet containing 0.6 protein/kg/IBW/day and 120-125/kJ/kg/IBW/day. LPD was randomly supplemented with KA at dosage of 100 mg/kg/IBW/day (61 patients, Group I) while 59 patients (Group II) received placebo. During the study period, glomerular filtration rate (GFR) slightly decreased (Ccr from 34.2±11.6 to 29.9±9.2 mL/min and 33.5±11.6 to 22.2±10.4 mL/min in Group I and II, respectively); this however was more marked in Group II (p<0.01). Fat in muscle measured by MR spectroscopy (MRS, m.tibialis anterior) significantly decreased in Group I and was linked to reduced volume of visceral fat measured by MRI (p<0.01). Reduction of fat in Group II was not significant. In Group I, there was a significant decrease in the plasma level of ADMA (from 2.4±0.4 to 1.2±0.3 μmol/L, p<0.01), but ADMA remained unchanged in Group II. A further remarkable finding was reduction in the plasma concentration of pentosidine (from 486±168 to 325±127 μg/L, p<0.01) and decrease of proteinuria (from 3.7±2.20 to 1.6±1.2 g/24hrs, p<0.01) in Group I. Plasma adiponectin (ADPN) in Group I rose (p<0.01). Analysis of lipid spectrum revealed a mild yet significant decrease in total cholesterol and LPD-cholesterol (p<0.01), more pronounced in Group I. In Group I, there was a decrease in plasma triglycerides (from 3.8±1.5 down to 2.3±0.5 mmol/L, p<0.01), whereas glycated hemoglobin (HbAc1) decreased from 7.0±1.3 to 4.1±0.9 %, (p<0.01) nIn conclusion,comparing to placebo group long term co-administration of LPD and KA in CKD patients led to decrease of ADMA,fat in muscle and visceral body fat, and proteinuria. Concomitant decreases of glycated haemoglobin, LDL-c and pentosidine may also contribute to the delay in progression of renal failure and decrease of cardiovascular risk factors..The study was supported by Research Project MZO 00023001 awarded by Ministry of Health of the Czech Republi

The relationship between estimated GFR based on the CKD-EPI formula and renal inulin clearance in potential kidney donors

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Do Ketoanalogues Still Have a Role in Delaying Dialysis Initiation in CKD Predialysis Patients?

Early versus later start of dialysis is still a matter of debate. Low-protein diets have been used for many decades to delay dialysis initiation. Protein-restricted diets (0.3-0.6g protein/kg/day) supplemented with essential amino acids and ketoanalogues (sVLPD) can be offered, in association with pharmacological treatment, to motivated stage 4-5 chronic kidney disease (CKD) patients not having severe comorbid conditions; they probably represent 30-40% of the concerned population. A satisfactory adherence to such dietary prescription is observed in approximately 50% of the patients. While the results of the studies on the effects of this diet on the rate of progression of renal failure remain inconclusive, they are highly significant when initiation of dialysis is the primary outcome. The correction of uremic symptoms allows for initiation of dialysis treatment at a level of residual renal function lower than that usually recommended. Most of the CKD-associated complications of cardiovascular and metabolic origin, which hamper both lifespan and quality of life, are positively influenced by the diet. Lastly, with regular monitoring jointly assumed by physicians and dietitians, nutritional status is well preserved as confirmed by a very low mortality rate and by the absence of detrimental effect on the long-term outcome of patients once renal replacement therapy is initiated. On account of its feasibility, efficacy and safety, sVLPD deserves a place in the management of selected patients to safely delay the time needed for dialysis

Adherence to ketoacids/essential amino acids-supplemented low protein diets and new indications for patients with chronic kidney disease.

BackgroundLow protein diets (LPD) have long been prescribed to chronic kidney disease patients with the goals of improving metabolic abnormalities and postpone the start of maintenance dialysis.MethodsWe reviewed the recent literature addressing low protein diets supplemented with ketoacids/essential aminoacids prescribed during chronic kidney disease and their effects on metabolic, nutritional and renal parameters since 2013.ResultsWe show new information on how to improve adherence to these diets, on metabolic improvement and delay of the dialysis needs, and preliminary data in chronic kidney disease associated pregnancy. In addition, data on incremental dialysis have been reviewed, as well as potential strategies to reverse protein energy wasting in patients undergoing maintenance dialysis.ConclusionThese recent data help to better identify the use of low protein diets supplemented with ketoacids/essential aminoacids during chronic kidney disease