Valorización de Activos y Pasivos

To date there has been no published work on the use of Gum Arabic in earlier stages of chronic kidney disease, but there are theoretical reasons behind benefits of its use. The areas in which I would like to concentrate are those looking at non renal clearance of urea that is seen with dietary fibres, its effects on glomerular filtration rate and effective renal plasma flow and its potential for affecting transforming growth factor beta (TGF- β) expression that could provide longer term benefits. The action of Gum Arabic on TGF-β may also be of benefit in the shorter term as well as long term by its effects on blood pressure homeostasis.

The use of Gum Arabic in an end stage renal failure population has not been studied in a randomised controlled trial. However, accessibility to renal replacement therapy in the developing world is limited and other treatment modalities that can postpone the time to initiation of renal replacement therapy are of great value. Al-Mosawi describes 4

paediatric patients [157, 158] who had reached end stage renal disease, and in whom access to renal replacement therapy was difficult. All patients’ diets were supplemented with powdered acacia gum (Gum Arabic). This was at a dose of 1g/kg in 3 of the patients and 0.5g/kg in the other patient. Intermittent peritoneal dialysis (IPD) was used as an adjunctive therapy if the patients became overtly symptomatic of uraemia. Three of the 4 patients showed stability of their renal function and a probable improvement in urea and creatinine. In one patient, its effect on blood pressure was also considered and,

57 although only anecdotal evidence appears to show an improvement in blood pressure that was reversed on cessation of treatment.

Nasir showed that gum arabic treatment in mice was associated with an increase in 24 hour urinary creatinine clearance. The mechanism is unclear but suggests a remote effect of gum arabic on the kidney and not that of non renal nitrogen clearance [159]. In a study of patients with CKD, the concentrations of creatinine, urea, phosphate and uric acid have been reported to be significantly lower in subjects give gum arabic at a dose of 50g/day for 3 months Possible mechanisms whereby Gum arabic may have these beneficial effects are discussed in the chapters following.

1.13.3.1 Non renal clearance of nitrogen

Bliss et al conducted a prospective, randomised, placebo controlled, single blinded study of a crossover design in 20 patients with chronic renal failure. The non placebo arm received 25g of Gum Arabic twice daily. They clearly showed that the mean nitrogen content of stool was significantly greater when taking Gum Arabic as compared to placebo or to baseline. In addition, serum urea nitrogen was also lower when compared to placebo or baseline [160]. This effect is dependent on an increase in colonic bacterial growth. These bacteria produce ureases that hydrolyse urea to

ammonia and carbon dioxide. The ammonia that is produced is then used by the bacteria and incorporated in to bacterial proteins which are then excreted in the bacterial mass fraction of the faeces [156]. Renal function per se is of course not directly affected, the result being non renal clearance of urea via the bowel.

1.13.3.2 Antioxidant properties

Several studies have also shown a potentially protective effect of Gum Arabic against gentamicin nephrotoxicity in rats [161, 162], possibly in part through inhibition of the production of oxygen free radicals that cause lipid peroxidation.

58 The renoprotective effect of Gum Arabic seems to be independent of any effects that it may have on faecal bacterial ammonium metabolism [161, 163], although in one of these studies the improvements in serum urea and creatinine did not reach significance. There is however evidence that contradicts the theory that Gum arabic has significant antioxidant properties. Ali et al demonstrated in a rat model that administration of varying concentrations of Gum arabic in the drinking water did not change significantly levels of free radical scavengers [163].

1.13.3.3 Production of short chain fatty acids

A common feature of all mammals is extensive microbial fermentation of

polysaccharides in the hindgut. Large amounts of short chain fatty acids (SCFA) are produced, with concentrations of SCFA generally about 100 mmol/l [164]. Bacterial fermentation of dietary fibre-rich substrates in the colon results in the production of a variety of short chain fatty acids. The proportions of the different SCFAs produced is dependent on the type of dietary fibre ingested. Bourquin et al showed that in human subjects, ingestion of different dietary fibre rich substrates produced different quantities of SCFAs in the faeces. The fibre rich substrates that they tested, in 3 human

volunteers, were two varieties of oat hull fibre, Gum Arabic, carboxymethylcellulose (CMC), soy fibre, psyllium, and six blends containing oat fibre, Gum Arabic, and CMC in various proportions. Production of SCFA was directly proportional to the content of Gum Arabic in the substrates and overall, proportions of the SCFAs were acetate, propionate, and butyrate, produced in the molar proportion of 64:24:12 [165]. Gum Arabic when given to caecostomised pigs, has also shown increased levels of short chain fatty acid production, in particular acetate and butyrate. This further supports its potential as a prebiotic agent [166].

Short chain fatty acid production has been shown to have certain health benefits, particularly improved bowel health. Butyrate in particular plays a central role in maintaining the mucosal barrier in the gut. A lack of SCFA may be the cause of ulcerative colitis and other inflammatory conditions. Butyrate has also been shown to increase wound healing and reduce inflammation in the small intestine. Importantly

59 butyrate is the dominant energy source for epithelial cells and affects cellular

proliferation and differentiation by yet unknown mechanisms [167]. It may also reduce the risk of colon cancer, and substrates that can decrease the acetate: propionate ratio may reduce serum lipids and possibly cardiovascular disease risk [168].

Gum arabic is able to selectively raise the proportions of different bifidobacteria in human intestinal microbiota, depending on the exact preparation of Gum arabic used. As a result levels of the short chain fatty acids butyrate and propionate are seen to rise [169].

Kishimoto et al have shown that SupergumTM (a specific preparation of Gum arabic) is fermented to short chain fatty acids by intestinal bacteria and that the dominant bacteria which is likely to be responsible is Prevotella ruminicola [170].

The possible health benefits of fibre as a result of short chain fatty acid production are clear but evidence currently only shows some benefit in the GI tract and possible

cardiovascular benefits. It is possible that dietary fibre, including Gum arabic has health benefits beyond the GI tract which could impact on diabetic nephropathy.