A Historical Perspective on Uremia and Uremic Toxins

Abstract

Uremia, also known as uremic syndrome, refers to the clinical symptoms in the final stage of renal failure. The definition of the term has changed over time due to an improved comprehension of the kidney's function and the advancement of dialysis technology. Here, we aim to present an overview of the various concepts that have developed regarding uremia throughout the years. We provide a comprehensive review of the historical progression starting from the early days of Kolff and his predecessors, continuing with the initial research conducted by Niwa et al., and culminating in the remote sensing hypothesis of Nigam. Additionally, we explore the subsequent investigation into the function of these toxins as signaling molecules in various somatic cells.

Keywords: dialysis; remote sensing and signaling; uremia.

Figure 1

Our understanding of uremia has evolved over time. Three main periods can be recognized. The first era is considered as the nascence of uremic intoxication. The second era starts after the development of dialysis as a clinical treatment for individuals affected by kidney failure. Uremia was seen as a remnant syndrome due to the incomplete removal of accumulated toxic waste substances. The current era of uremia research is based on molecular signaling cascades.

Figure 2

From left to right: Portrait of Hippocrates from Linden, Magni Hippocratis 1665 Wellcome Library, London; Vascular system from Bartolomeo, Eustachio T‘abulae Anatomicae’, edited by J.M. Lancisi, 1714 Wellcome Library, London; Portrait of Richard Bright, 1838, Great Norwegian Encyclopedia Bergen; Photo of Kolff’s artificial kidney, Museum Boerhaave, Leiden; Chemical structure of indoxyl sulfate, PUBCHEM, National Library of Medicine; Publication of NCDS study [23], PUBMED, National Library of Medicine; European uremic toxin group logo; 3-dimensional structure of OAT3 (SLC22A8), GeneCards, The Human Gene Database; Publication of uremic syndrome of chronic kidney disease [4], PUBMED, National Library of Medicine. All images available under Creative Commons license.