RT info:eu-repo/semantics/doctoralThesis
T1 Toxinas Urémicas Unidas a Proteínas en Hemodiálisis. Estrategias de depuración: Función Renal Residual y Desplazadores
A1 Sánchez Ospina, Didier
A2 Universidad de Valladolid. Escuela de Doctorado
K1 Internal medicine
K1 Chronic kidney disease
K1 Enfermedad renal crónica
K1 32 Ciencias Médicas
AB AbstractProtein-bound uremic toxins (PBUTs) remain one of the most persistent and least resolved challenges in renal replacement therapy. Unlike small solutes such as urea, PBUTs have a high affinity for albumin, which severely limits their clearance through glomerular filtration or conventional hemodialysis. Their accumulation has been linked to endothelial dysfunction, chronic inflammation, cardiovascular events, and disease progression. Yet, their clinical evaluation and therapeutic management remain inconsistent and poorly integrated into routine nephrology practice.This doctoral thesis explores the behavior of three major PBUTs —p-Cresyl sulfate, indoxyl sulfate, and hippuric acid— across different clinical settings in chronic kidney disease patients on hemodialysis. The first study characterizes plasma levels of these toxins in a large cohort of anuric patients undergoing online hemodiafiltration. The second examines the relationship between blood and urinary levels of PBUTs in a subgroup of patients with preserved residual renal function receiving incremental hemodialysis. Finally, a crossover study evaluates the effect of two loop diuretics —furosemide and torasemide— on the dialytic clearance of PBUTs in anuric patients.Results show clear differences between toxins in terms of accumulation and response to intervention. Residual renal function, even when limited, plays a significant role in PBUT elimination, mainly through tubular secretion. Furthermore, loop diuretics were shown to enhance the clearance of PBUTs by displacing them from albumin-binding sites, increasing their free circulating fraction and making them more available for dialysis removal.Together, these findings call for a redefinition of traditional adequacy markers in dialysis when PBUTs are involved. Preserving residual renal function, incorporating pharmacological strategies such as loop diuretics, and tailoring dialysis protocols to individual physiological profiles appear essential for improving the management of these under-recognized toxins. A deeper understanding of PBUT dynamics opens the door to more physiologically aligned and patient-centered renal therapies.
YR 2025
FD 2025
LK https://uvadoc.uva.es/handle/10324/76281
UL https://uvadoc.uva.es/handle/10324/76281
LA spa
NO Escuela de Doctorado
DS UVaDOC
RD 30-jul-2025