PROGRESS IN UREMIC TOXIN RESEARCH: The General Picture of Uremia

Abstract

The clinical presentation and manifestations of uremia that constitute the uremic syndrome are presented. The first descriptions of patients with advanced or "terminal" renal failure who were treated with hemodialysis are evoked to illustrate the wide range of signs and symptoms that are associated even to a moderate decrease in renal function, presently referred to as chronic kidney disease (CKD) stages 3-4. The kidney is a central organ guaranteeing the maintenance of the "milieu intérieur," where all the cells of the body are generated, develop, proliferate, and die. Chronic kidney disease, by altering the "milieu intérieur," may alter the metabolism of every type of cell or organ, leading to a wide scope of symptoms. The most frequently observed signs in daily clinical practice are summarized and put into the perspective of the renal physician. Disturbances of ion and water metabolism, hypertension, cardiovascular disease, anemia, mineral and bone disorders, endocrine, inmmunologic and neurologic syndromes are described. The addition of these clinical manifestations defines and describes each uremic patient as a specific individual. The pathophysiologic mechanisms by which each of these signs and symptoms appears and the particular compounds responsible for their occurrence, are described in depth in subsequent chapters of this issue.

Alteration of human blood cell transcriptome in uremia

“…Dialysis may ameliorate the symptoms of uremia, but inadequate clearance of uremic toxins ultimately results in progressive illness manifest by chronic injury to the vascular tree, skeleton, neuronal networks and other critical bodily systems [1,2]. The European Uremic Toxin Work Group has listed more than 100 retained solutes that variably impair cellular function or survival and are important contributors in the expression of uremia [16].…”

“…Pleomorphic manifestations of uremia appear as renal function declines, and include impaired cognition and execution of higher function tasks; disordered neuromuscular function with muscle weakness, seizures and sensorimotor neuropathy; altered endothelial function with accelerated vascular disease; hematological alterations with anemia, platelet dysfunction and bleeding; endocrine and metabolic disorders typified by insulin resistance, gonadal dysfunction, hyperparathyroidism, bone disease and soft-tissue calcification; and disorders of innate and adaptive immunology with features of both inflammation and immune deficiency [1,2]. …”

Impact of Hemodialysis Therapy on Anemia of Chronic Kidney Disease: The Potential Mechanisms

“…PTH is considered as a major MM uremic toxin with multiple biological effects, including causing anemia by a direct inhibitory effect on endogenous EPO synthesis, bone marrow erythroid progenitors (suppressing erythropoiesis) and RBC survival [31]. PTH also affects the response to exogenous ESA in HD patients; secondary hyperparathyroidism has been identified to increase EPO resistance [3,32]. PTH levels, together with markers related to anemia correction, inflammation, oxidative stress and hyperphosphatemia, were compared for OL-HDF and LF-HD in a crossover study with 70 patients [33].…”

The Effectiveness of an Educational Intervention on Fatigue in Hemodialysis Patients: A Randomized Controlled Trial

“…Patients on hemodialysis account for approximately 92% of the overall dialysis population [1] and endure a high symptom burden as they may experience troubling symptoms such as fatigue, decreased appetite, trouble concentrating, swelling in their feet and hands, muscle cramps, and itching. [2][3][4] , all of which cause daily distress and negatively affects their quality of life. [5,6] Haemodialysis plays an important role in maintaining renal function.…”