Formació, transformació i inhibició de nefròlits d'oxalat de calci: estudis in vitro i especiació per tècniques de radiació de sincrotró
- Autores: Iris de la Trinidad Henríquez Valido
- Directores de la Tesis: Montserrat López Mesas (dir. tes.)
- Lectura: En la Universitat Autònoma de Barcelona ( España ) en 2021
- Idioma: catalán
- Tribunal Calificador de la Tesis: Dominique Bazin (presid.), Fèlix Grases Freixedas (secret.), Roswitha Siener (voc.)
- Programa de doctorado: Programa de Doctorado en Química por la Universidad Autónoma de Barcelona
- Materias:
- Enlaces
- Tesis en acceso abierto en: TDX
- Resumen
Nephrolithiasis is a painful disease caused by calculi formation in the kidney. It has an incidence of around 5-12% and a recurrence with a relapse rate of 50% in 5 years and 80-90% in 10 years, generating millions of euros per year of expenses for the health care system. Kidney stones are classified into seven major groups by morpho-constitutional analysis guidelines, where calcium oxalate stones, considering both the mono- (COM) and the dihydrated (COD) species, represents around 60-70%, being the most prevalent type. However, due to its low stability, COD suffers a crystalline conversion (transformation) into COM, which is the thermodynamically stable species. Hence, calcium oxalate monohydrate in renal calculi can be either formed directly as COM or as the resulting product after the transformation from COD (hereafter named TRA). These different formation origins are related with different pathologies, for example, COM is usually related to hyperoxaluria while COD is related to hypercalciuria.
The aim of the multidisciplinary work presented in this Thesis Dissertation is to understand the basis behind the stone formation, crystalline conversion and inhibition of calcium oxalate nephroliths by the application of in vitro studies, as well as to determine the speciation of these species, in the renal calculi by using synchrotron radiation based techniques. To achieve the main goal, the work is presented in six studies: 1. The characterization of synthetic calcium oxalate hydrates by X-ray diffraction (XRD), X-ray absorption spectroscopy (XAS), infrared (IR) and raman spectroscopy, and the application of a density functional theory (DFT) computational study with the objective of performing an unambiguous assignment of the vibrations, thus providing the appropriate parameters required to monitor and characterize the COD transformation process.
2. Determination of organic matter (proteins and lipids) distribution along the oxalocalcic calculi by synchrotron-based IR microspectroscopy, in order to stablish their role as promoters or inhibitors in the stone formation, as well as their participation in the stabilization of COD.
3. Distinguish the formation origin of calcium oxalate monohydrate in stones with the application of synchrotron microdiffraction, resolving it with the analysis of the 2D diffraction patterns and its correlation with the level of texture of COM and TRA.
4. Study the effect of common urine inhibitors in the COD crystalline conversion by in vitro incubations in synthetic media containing citrate, magnesium, phosphate or phytate, and their combinations with calcium, which will help to better understand the COD transformation and stabilization processes in urine.
5. Development of a new fast and affordable risk index, Urine Inhibitory Capacity (UIC), which is related with the capacity of the urine inhibitors to interact with the promoters and avoid the formation of calcium oxalate crystals. It is presented in comparison with the Relative Supersaturation (RSS) since it presents a two major drawbacks: the amount of analytical work required to determine it and the wide “grey zone” of values between stone formers and healthy subjects (range of data that comprehend both groups).
6. Study of the antioxidative properties and the effect of different extract fractions from a plant traditionally used as kidney stone breaker and diuretic on the Canary Islands, Lepidium latifolium L., also known as “rompepiedras” (“stone breaker”), on the calcium oxalate formation. With the preliminary results, the extracts derived from this plant could be considered as a potential treatment and/or prevention of oxalocalcic kidney stones.
