Contribution to lithiasic process knowledge. Characterization of physiological aspect and novel material to determine key inhibitors

Student thesis: Doctoral thesis

Abstract

Urolithiasis is one of the most prevalent urological diseases, occurring in both industrialized and developing countries. The incidence rate is up to 15% of white men and 6% of all women and the recurrence affect about half of those people. Kidney stones are aggregates of crystals that cause obstruction of urine flow in the renal collecting system, ureters, or urethra and result in severe pain, bleeding or local erosion of kidney tissue. The etiological diversity of urinary stone formed as a result of different mechanisms which is still not well understood. The challenges posed by urinary lithiasis demands enhanced interdisciplinary diagnostic, therapeutic options and secondary prevention. The purpose of this thesis is to offer knowledge to the previous mentioned challenges using novel scientific methods or materials. The dissertation exposes the work developed in three areas concerning urolithiasis, which embeds urolithiasis key inhibitors extraction from food, phosphorous inhibitors determination by using novel material, and copper isotopic fractionation analysis from urolithiasis patients The first section in the dissertation is devoted to the use of microwave assisted extraction (MAE) technique to quantitatively extract the two phosphorous inhibitors of urolithiasis, phytic acid (IP6) and pyrophosphate (PPi), from walnut since the existing extraction method and quantitative analysis show inconveniences. Walnuts were chosen since they are highly consumed, rich in polyunsaturated fatty acid and provide significant benefits due to the antioxidant capacity. Three main parameters were considered to optimize the condition of microwave-assisted extraction: acid content of extracting solvent, extraction time and treatment temperature. The hydrolysis of phytic acid by microwave treatment was also investigated for all the tested conditions. The extraction using mixture of 0.52 M H2SO4 and 0.66 M HCl under MAE condition (100°C, 10min) shows a better extract ability for both IP6 and PPi. Compared with the conventional acid extraction method, the microwave-assisted extraction method developed reduces extraction time from 3h to 10 min obtaining the same recovery results. The second section in the dissertation is devoted to develop a novel material based on molecular imprinted technology for selectively adsorb and separate the IP6 and PPi. In this work, polymers have been molecularly imprinted using three organophosphorus compounds as template, phenylphosphonic acid (PA), Di-(2-ethylhexyl) phosphoric acid (DEHPA) and pyrophosphoric acid. The Molecularly Imprinted Polymer, MIP, was prepared by thermal polymerization using Nallylthiourea (AT) as functional monomer and ethylene glycol dimethacrylate (EGDMA) as crosslinker. The batch adsorption experiments show that the MIP using DEHPA has the best specific adsorption for IP6 and the adsorption process is quite fast. The pH has a significant effect on the adsorption behavior of IP6, PPi and phosphate. Through modification of the pH of the eluting solvent, IP6, PPi and phosphate can be separated by SPE procedure using the developed MIP. The third part of the thesis considers the physiological aspect of urolithiasis. In the literature Copper has shown inhibitory effect on the growth of kidney stone and disordered in copper metabolism may be important in the aetiology of disease. The blood Copper isotope fractionation from urolithiasis patients from Barcelona area was analyzed and compared to healthy controls. The serum and red cell samples Cu isotope compositions was measured by multi-collector ICP-MS after separation and purification by anion exchange chromatography. Our results show that, for the population considered in this study, Cu concentration and Cu isotopic ratio (65Cu/63Cu) show different value between the urolithiasis patients and the healthy people. Although further studies with a larger number of samples are needed, results are encouraging as far as the use of Cu isotopic analysis for the study of urolithiasis disease.
Date of Award25 Nov 2015
Original languageEnglish
Awarding Institution
  • Universitat Autònoma de Barcelona (UAB)
SupervisorManuel Valiente Malmagro (Director) & Montserrat López Mesas (Director)

Cite this

'