DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for uremia — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleUremia maps to a 1-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for uremia is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
nuclear receptor subfamily 3 group C member 1 (NR3C1) — NR3C1 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet adpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7KW7 · 3.57 Å · ligand ADENOSINE-5'-DIPHOSPHATE (ADP). Experimental structure, not a prediction.
What the evidence adds up to
The 2008 review states that mortality in end-stage renal disease remains unacceptably high. It identifies p-cresol sulfate and indoxyl sulfate as small, protein-bound uremic toxins that are poorly cleared by dialysis and have been linked to cardiovascular disease and oxidative injury. Impaired immunity is described as both a result of uremic toxicity and a contributor to oxidative stress. Uremic cachexia is noted as an underrecognised syndrome, and the review mentions that new insights into disordered feeding circuits might lead to therapies using hormone agonists, but no such therapy is tested or proven in the abstracts provided.
The 1990 piece quotes Sir William Osler’s observation that the nature of the poisonous ingredients in uremia was not yet known, and notes that nearly a century later Ruiz and colleagues used modern immunologic techniques to investigate one aspect of the uremic syndrome. The 2024 historical review traces the changing definition of uremia from Kolff’s early work through Niwa’s research to Nigam’s remote sensing hypothesis, and describes subsequent investigation into uremic toxins as signalling molecules in somatic cells. The 1956 book review and the 1947 paper on peritoneal lavage describe older therapeutic principles and the use of a temporary kidney substitute, but provide no quantitative outcomes.
No drug is mentioned in any of these abstracts. No trial data, response rates, or survival figures are given. What is missing is any controlled clinical trial of a specific pharmacological intervention for uremia, any patient stratification strategy, and the funding needed to move from descriptive toxin identification to a tested treatment.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in Nephrology & Hypertension · 2008 · 90 citations
New insights into uremic toxicity
AbstractPURPOSE OF REVIEW: Our concept of uremia has expanded to encompass the illness patients begin to suffer as glomerular filtration rate declines long before the onset of end-stage renal disease (ESRD) not explained by known derangements in volume status or metabolic parameters. New insights into the accumulation of uremic toxins and the loss of function of hormones and enzymes provide important information on the etiology of uremia. RECENT FINDINGS: New data are accumulating on the identity and toxicity of uremic toxins and the syndromes that encompass uremia. rho-Cresol sulfate and indoxyl sulfate are small, protein-bound molecules that are poorly cleared with dialysis. These molecules have been linked to cardiovascular disease and oxidative injury. Impaired immunity plays a central role in the morbidity of ESRD and may be both the result of uremic toxicity and a contributor to oxidative stress in ESRD. Uremic cachexia is an underrecognized uremic syndrome. New insights into disordered feeding circuits in ESRD may lead to novel therapies using hormone agonists. SUMMARY: Mortality in ESRD remains unacceptably high. It is hoped that as knowledge emerges on the causes and consequences of uremia, we are embarking on an era not only of new insights but also new and effective treatments for patients with the ill effects of uremia.
New England Journal of Medicine · 1990 · 72 citations
Uremia and Host Defenses
AbstractIN the first edition of his Principles and Practice of Medicine, Sir William Osler stated that the clinical manifestations of uremia are caused by the retention of the excretory products. The nature of these poisonous ingredients is not yet known. It was formerly thought that the urea was the offending substance, and it has been found increased in the blood in uraemia.... It is more probable, however, that there are several toxic agents at work.1 Nearly a century later, Ruiz et al.2 have employed modern immunologic techniques to investigate one important aspect of the uremic syndrome — the effects . . .
A Historical Perspective on Uremia and Uremic Toxins
AbstractUremia, 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.
American Journal of Clinical Pathology · 1956 · 9 citations
The Treatment of Renal Failure
AbstractThe Treatment of Renal Failure The Treatment of Renal Failure. Therapeutic Principles in the Management of Acute and Chronic Uremia. By Merrill John P., M.D., Associate in Medicine, Harvard Medical School and Peter Bent Brigham Hospital; Established Investigator, American Heart Association. 238 pp., 31 figs., 16 tables. $6.75. New York: Grune & Stratton, Inc., 1955. Harry Goldblatt Harry Goldblatt Cleveland, Ohio Search for other works by this author on: Oxford Academic Google Scholar American Journal of Clinical Pathology, Volume 26, Issue 12, 1 December 1956, Page 1469, https://doi.org/10.1093/ajcp/26.12.1469a Published: 01 December 1956
New England Journal of Medicine · 1947 · 6 citations
Treatment of Acute Uremia by Peritoneal Lavage
AbstractTHE treatment of uremia has long been directed toward symptomatic relief, healing of the underlying renal lesion and, in acute and presumably temporary cases, maintenance of life long enough to allow the kidneys to reassume their essential functions. It is toward the last objective that attempts have been made by numerous workers to supply a temporary "substitute" for the kidneys, which would maintain excretion of uremic metabolites, whose retention is fatal to the organism. In a review of the chemical changes known to occur in uremia, Harrison and Mason1 stressed the importance of increased blood and tissue concentrations of urea, . . .
Current Opinion in Nephrology & Hypertension · 1993 · 5 citations
Drugs and the kidney
AbstractRenal insufficiency affects every organ system and every aspect of drug disposition by the body. Because the kidney is the organ responsible for the elimination of most drugs or their metabolites from the body, renal dysfunction results in substantial changes in drug therapy. Furthermore, the kidney is often a target organ for the expected physiological effects of the drugs that are given or for their toxicity. Finally, our therapeutic options for treating uremia complicate drug therapy by further changing drug disposition. This article reviews recent work aimed at understanding these processes.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
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