Study of the Crystallization Inhibition Capacity of the Uric Acid in Urine in a Group of Lithiasic Patients After Intake of a Food Supplement. PEv2

Background Urolithiasis is a pathology known since antiquity although they are not known totally the causes of the formation of all the different types of calculus existing As a consequence of this, only in some cases has it been possible to develop an efficient treatment. Renal lithiasis affects a wide range of the population, varying from 4 to 15% according to the population sample studied. It is important to highlight the high morbidity associated with this pathology, since between 10 and 15% of cases require surgical treatment and between 20 and 30% it requires hospitalization. Among all lithiasis, it is estimated that uric lithiasis accounts for between 10 and 15% of all cases and especially affects men over 50 years old, while mixed lithiasis of calcium oxalate monohydrate and uric acid affects 2.5% of all the cases. Lithiasis generated by uric acid are a highly pathology recurrent, even repeating several times during the year, and is related with other pathologies such as diabetes and obesity. This implies a high cost estimated in billions of euros per year, especially for its incidence in medical emergencies. It should be noted that between 50 and 70% of people who do not receive treatment or do not change their nutritional habits develop new calculus in a period of time less than 5 years. Is a contracted fact that the type and characteristics of the feed will determine the functioning of the acid-base metabolism and the characteristics of the urine as it can be its pH, the greater or lesser concentration of substances, as well as a set of characteristics that can determine the crystallization capacity of the different substances contained in it such as uric acid. It is evident that the medical problem that lithiasis originates should not be treated so only eliminating the same one, by means of the different surgical techniques available, but also the alterations responsible for its use must be modified and corrected training. If these alterations are not modified, the risk of genesis of new calculus persists. The pharmacological treatments used so far for treat uric lithiasis are based on the powerful alkalinization of urine (by using of citrate or bicarbonate) increasing the urinary pH to avoid crystallization of the uric acid and the formation of new kidney stones. These treatments can present a long-term problem and as a consequence there is a low- 2 - percentage of adherence to the treatment of uric acid stones. These long-term treatments can increase urinary pH above 6 units and end up causing a different type of renal lithiasis, the phosphatic, a lot more difficult to treat, by increasing the possibility of total calcification of the kidney that it implies. Therefore, it is evident that new alternatives should be sought in substances of food source that could facilitate the dietary treatments of said pathology.

There are currently citrate-based food supplements on the market plant extracts that contribute to the normal functioning of the metabolism acid-base of the organism alkalizing the urine (for example Lit control pH up). But there are also other approaches to the problem of lithiasis based on avoiding or decreasing the crystallization capacity of urine developed by the Renal Lithiasis Research Laboratory of the University of the Illes Balears. These approaches consist in looking for inhibitors of the crystallization of natural origin A crystallization inhibitor corresponds to a substance that is able to prevent, delay or hinder the crystallization of insoluble compounds. This approach was already started with the work of Bliznakov in 1965, showing that certain molecules were able to slow down the growth rate crystalline nature of certain substances as a result of their adsorption (binding) on growth surfaces and the corresponding alterations that this caused. During this time Vermeulen et al., Fleisch et al. and Howard and cols showed that a series of substances present in the urine, including pyrophosphate, were capable to prevent the crystallization of the calcium salts. These ideas too were later developed by the Lithiasis Research Laboratory Renal observing that said inhibitory capacity of the crystallization of calcium salts It was also made by phytate, a substance that is present in all unrefined seeds (legumes, cereals, nuts, ...). This process led to the search for natural substances that presented said ability to inhibit, not on the crystallization of calcium salts but on the crystallization of uric acid. Among numerous substances used in the tests In vitro it was observed that theobromine, natural component of cocoa produces said effect concentrations similar to those produced after the usual chocolate intake. In Europe chocolate intake is approximately between 6 and 12 kg per person and year. For this reason, it is intended to reduce the inhibition capacity of the uric acid from the urine by an in vitro test after the intake of a supplement determined food For this purpose, urine samples from patients will be used volunteers who will supply to the Renal Lithiasis Research Laboratory assigned to the IUNICS (University of the Balearic Islands) before and after the intake of- 3 - a certain food supplement food for a time settled down.

Justification The Renal Lithiasis Research Laboratory since 1998 has as one of its its purpose is to study the relationship between the characteristics of urine and the different types of existing lithiasis. As we have indicated one of the lithiases with a large incidence is lithiasis of uric acid or calcium oxalate monohydrate / uric acid. Currently, the relationship between the ability to inhibit crystallization of uric acid from a urine after ingestion of certain food Complements.

Urine is a product of blood filtration that reflects its composition, including water and low molecular weight molecules such as salts, vitamins, minerals, etc. accordingly the intake of certain foods, such as the chocolate, cocoa or an extract thereof, will be reflected in an increase in urinary excretion of theobromine, an inhibitor of the crystallization of uric acid.

Due to this, the modification of the crystallization capacity of uric acid in the urine should be clearly reflected. Naturally, apart from this main variable, urine must be determined in series of secondary variables such as urinary pH, concentration of Theobromine and all other important urinary parameters in the pathology lithiasic.