BENEFICIAL EFFECT OF KETO AMINO ACIDS FOR DIALYSIS PATIENTS

Abstract

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.