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Abstract
CRF is a complex syndrome in which many factors other than absolute or relative Erythropoietin deficiency may contribute towards causing anaemia. (Eschbach JW, 1989)
Although iron deficiency is probably the most important factor affecting the response to rHuEpo in most patients, occult blood loss, infection, and inflammation are also important. (H?rl WH, 1999)
Less frequent are problems of hyperparathyroidism with marrow fibrosis, aluminum toxicity, vitamin B12 and folic acid deficiency, haemolysis, bone marrow disorders, haemoglobinopathies, dialysis, and carnitine deficiency. (Kletzmayr J et al., 1999) ACE inhibitors and angiotensin II receptor antagonists may also play a role. (Albitar S et al., 1998)
Thus, a still unknown uraemic toxin may suppress erythropoiesis and contribute towards the development of anaemia. It is reasonable to postulate low-molecular-weight erythroid inhibitors (because anaemia improves after the start of dialysis with cellulose membranes) and possibly medium-to large-molecular-weight inhibitors of 10 000 Daltons only removed by more permeable membranes. (Niwa T et al., 1990)
Uremia is also characterized by the retention of protein-bound solutes that have an effective molecular size the
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same as that of their carrier protein. Many small protein-bound solutes are retained in chronic kidney disease (Vanholder R et al., 2003), and some of these have been demonstrated to exert a toxic effect at the concentrations observed in ESRD. For example, 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (240 Da), which is 98% bound to albumin, inhibits erythropoiesis (Niwa T et al., 1990),
Whether haemodialysis removes these toxins (which still their nature are not known) is still a matter of debate.
HD, far from improving the oxidative status, results in an enhancement of ROS owing to hemoincompatibility of the dialysis system, hemoreactivity of the membrane, and trace amounts of endotoxins in the dialysate. In addition, the HD process is associated with an impairment in antioxidant mechanisms. The resulting oxidative stress has been implicated in long-term complications including anemia, amyloidosis, accelerated atherosclerosis, and malnutrition. (Morena M et al., 2005)
The erythrocyte life span in chronic renal failure decreases with progressive severity of uraemia and may be reduced to one-third of normal. (Loge et al . 1958 )
It was well known that affection of osmotic fragility of RBCs in these uraemic patients was at least considered one of the possible causes of mild haemolytic state in these patients that may contribute to their short life span.
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In our study, we found that all our patients are anaemic with mean predialysis Hb = 8.86 gm% ± 2.44, as well as low haematocrit %( mean 27 ± 7.6) as shown in table 8.
Also in our patients, the mean pre-dialysis starting point of osmotic fragility (mean 0.51 ± 0.09) was significantly higher when compared to control group (mean = 0.45) (table 8).
However, the mean predialysis complete point of osmotic fragility was showing slight higher significance when compared to control (table 8).
Both starting and complete points of osmotic fragility were markedly improved (decreased) after haemodialysis if compared to pre-dialysis levels (table 10).
This improvement in osmotic fragility post-dialysis may be due to possible removal of unidentified uraemic toxins that may affect the osmotic fragility.
However, it was well known that uraemic plasma almost contains toxins that inhibit Na-K pump of all cells of the body especially of RBCs.
We suggest that removal of these toxins that affect Na-K pump of RBCs membrane by the haemodialysis process may be responsible for the improved osmotic fragility of RBCs in our patients after haemodialysis which did not show significant difference if compared to control group (table 9).
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L-Carnitine is a naturally occurring compound that facilitates the transport of fatty acids into mitochondria for beta-oxidation. B-oxidation of fatty acids proceeds which yields energy in the form of ATP. ATP is required for Na+?K+ ATPase and to maintain the structural integrity of RBCs biconcave disc shape and without ATP there is swelling and lysis of the cells resulting in fragility of RBCs. (Eaton S, et al. 1996)
Circulating free fatty acids are endogenous inhibitors of the Na+-K+-ATPase. L-Carnitine increases delivery of free fatty acid to the mitochondria for oxidation and as a result the plasma concentration of free fatty acids decreases and the inhibition of the Na+-K+-ATPase is reversed. (Jürgen Bommer, 1999)
A lack of carnitine in hemodialysis patients is caused by insufficient carnitine synthesis and particularly by the loss through dialytic membranes, leading, in some patients, to carnitine depletion with a relative increase in esterified forms. (Matera M et al., 2003)
Red blood cells (RBCs) in HD patients contained a comparable level of carnitine to normal controls, despite the presence of serum carnitine deficiency, and that RBC carnitine was not removed through HD, in contrast to serum carnitine. These results suggest that RBC carnitine may be essential for RBCs to perform their metabolic function in renal anemia and that oral L-carnitine treatment could improve anemia in poor responders to EPO. (Matsumoto Y et al., 2001)