Intracellular free amino acids and nutritional status in children with chronic renal failure on different treatments

Detta är en avhandling från Stockholm : Karolinska Institutet, Department of Clinical Sciences

Sammanfattning: In untreated adult patients with chronic renal failure (CRF), and in chronic ambulatory petitoneal dialysis (CAPD) and kidney-transplanted patients, typical plasma and muscle intracellular amino acid (AA) patterns have been described. Similar AA abnormalities to those seen in adult patients have been observed in plasma and muscle tissue of children with CRF, but no studies have been undertaken to evaluate the AA levels in plasma and muscle in children on CAPD or after kidney transplantation. Polymorphonuclear granulocytes (PMN) are valuable tools for evaluating AA metabolism in nucleated cells but an error in PMN AA concentration may be induced by Increase activation during the analytical procedure. Red blood cells (RBC) contain a large proportion of the free AA in the blood and are actively involved in the inter-organ transport of AA- The AA profile in RBC has been reported abnormal in patients with CFR There are no studies in which AA concentrations in PMN have been compared with muscle or RBC concentrations. In this thesis anthropometric measurements, plasma and muscle proteins and AA were determined in children with CRR, in children on CAPD and in kidney-transplanted children. The results were compared with data from healthy age-matched children. A reliable method for AA determination in PMN was set up and comparison between intracellular AA in muscle, RBC, PMN and plasma were done in CRF children. In study I, before the start of dialysis 15 children with CRF were investigated with anthropometric measurements and determination of plasma proteins, muscle alkali-soluble proteins (ASP) and AA. The results were compared with data obtained from 10 age-matched control children. The nutritional parameters were normal in the CRF children, suggesting that a satisfactory nutritional status can be maintained during conservative treatment. However, they exhibited several AA abnormalities in plasma and muscle typical of uremia. In study 11, 10 children on CAPD were investigated with anthropometric measurements and determination of plasma and muscle proteins and AA. The results were compared to data obtained from 22 age-matched control children. The findings of a compromised nutritional status, reduced plasma levels of most essential AA and low muscle valine and leucine concentrations suggests that they may potentially benefit from AA supplementation to improve protein malnutrition. In study 111, 13 kidney-transplanted children were investigated with anthropometric measurements and plasma and muscle proteins and AA determinations and the results were compared to data obtained from 10 age- matched control children. The transplanted children showed an almost normal muscle AA profile, whereas the plasma AA pattern exhibited minor abnormalities, which seem to be related to the prednisone therapy. In study IV, proteolytic activity and PMN AA were determined in blood samples processed with and without anti-proteolytic agents in 10 adult volunteers. PMN AA concentrations and protease activity in samples treated with anti-proteolytic agents were 8 to 10 times lower than in samples processed without anti-proteolytic agents. Hence, prevention of proteolysis during the sample preparation is necessary for reliable estimation of free AA in PMN. In study V, anthropometric measurements, plasma and muscle proteins, plasma, RBC, PMN and muscle AA were studied in 12 chronically uremic children and the results compared to data obtained from 13 agematched normal children. The lack of correlation between the concentrations in RBC, PMN and muscle for most of the AA in the same subject may be due to differences in metabolism and function of these cells. In consequence, one should be cautious in assuming that AA concentrations, determined in PMN, reflect the concentrations in muscle cells, as previously suggested, although in groups of subjects the general AA pattern in these nucleated cell types are similar. In summary, this thesis has demonstrated that 1) children with CRF, on CAPD and kidney transplanted show typical plasma and muscle AA abnormalities, 2) the use of anti-proteolytics during the sample preparation is necessary for reliable estimation of free AA in PMN 3) although in groups of subjects the general AA pattern in PMN and muscle may be similar it is hazardous assuming that AA concentrations, determined in PMN, reflect the concentrations in muscle cells.

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