DeCure's autonomous Nephrology AI scientist is researching a drug-repurposing hypothesis for urinary system disease — screening already-approved drugs against its 42-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleUrinary system disease maps to a 42-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 urinary system disease 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
intersectin 2 (ITSN2) — ITSN2 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 unxdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3JZY · 1.56 Å · ligand UNKNOWN ATOM OR ION (UNX). Experimental structure, not a prediction.
What the evidence adds up to
A 2017 AUA white paper defined nonneurogenic chronic urinary retention as a post-void residual above 300 mL persisting at least six months and documented twice. It proposed stratifying patients first by risk (high risk meaning hydronephrosis, stage 3 chronic kidney disease, or recurrent culture-proven urinary tract infection or urosepsis) and then by symptoms (symptomatic meaning moderate to severe quality-of-life impact or recent catheterisation). Four primary outcomes were suggested for judging treatment: symptom improvement, risk reduction, successful voiding without a catheter, and stability of symptoms and risk over time. The paper offered no new clinical data; it was a consensus framework intended to spur comparative research.
A 2006 review of urinary tract infection pathogenesis described the urothelium as an anatomical barrier that expresses toll-like receptors. Engagement of these receptors can trigger production of inflammatory mediators including complement, cytokines, chemokines, defensins, and adhesion molecules. The resulting inflammatory infiltrate helps clear bacteria but can also cause renal damage. The review noted that polymorphisms in candidate genes of the host defence system may determine which patients are susceptible to recurrent infections and renal scarring. It offered no therapeutic intervention and no patient-level outcomes.
A 2015 laboratory study examined whether inflammasomes are involved in urothelial defence against uropathogenic E. coli. Primary human urothelial cells and bladder cancer cell lines expressed NLRP3 at high levels. Exposure to NLRP3 ligands (lipopolysaccharide, flagellin, ATP) and to type 1-piliated UPEC strains (UTI89, CFT073, NU14) induced secretion of IL-1β and IL-18, cleavage of pro-caspase-1, and release of lactate dehydrogenase, all hallmarks of NLRP3 inflammasome activation. Knockdown of NLRP3 by shRNA, or addition of the NLRP3 inhibitor glybenclamide or a caspase-1 inhibitor, significantly blunted this activation. The study was entirely in vitro; it did not test any drug in patients, report any clinical response, or measure survival or infection rates in humans.
What is missing for any of these findings to change clinical practice: the 2017 white paper explicitly calls for comparative research that does not yet exist; the 2006 review identifies no specific drug target that has been validated in patients; the 2015 study is confined to cultured cells and has not been translated into a clinical trial. No funding for a repurposing trial in urinary system disease is described, no patient stratification beyond the white paper’s risk/symptom categories has been prospectively tested, and no drug mentioned in these abstracts has been shown to improve outcomes in humans with chronic urinary retention or recurrent urinary tract infection.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
The Journal of Urology · 2017 · 126 citations
AUA White Paper on Nonneurogenic Chronic Urinary Retention: Consensus Definition, Treatment Algorithm, and Outcome End Points
AbstractPURPOSE: The AUA (American Urological Association) QIPS (Quality Improvement and Patient Safety) committee created a white paper on the diagnosis and management of nonneurogenic chronic urinary retention. MATERIALS AND METHODS: Recommendations for the white paper were based on a review of the literature and consensus expert opinion from the workgroup. RESULTS: The workgroup defined nonneurogenic chronic urinary retention as an elevated post-void residual of greater than 300 mL that persisted for at least 6 months and documented on 2 or more separate occasions. It is proposed that chronic urinary retention should be categorized by risk (high vs low) and symptomatology (symptomatic versus asymptomatic). High risk chronic urinary retention was defined as hydronephrosis on imaging, stage 3 chronic kidney disease or recurrent culture proven urinary tract infection or urosepsis. Symptomatic chronic urinary retention was defined as subjectively moderate to severe urinary symptoms impacting quality of life and/or a recent history of catheterization. A treatment algorithm was developed predicated on stratifying patients with chronic urinary retention first by risk and then by symptoms. The proposed 4 primary outcomes that should be assessed to determine effectiveness of retention treatment are 1) symptom improvement, 2) risk reduction, 3) successful trial of voiding without catheterization, and 4) stability of symptoms and risk over time. CONCLUSIONS: Defining and categorizing nonneurogenic chronic urinary retention, creating a treatment algorithm and proposing treatment end points will hopefully spur comparative research that will ultimately lead to a better understanding of this challenging condition.
Current Opinion in Pediatrics · 2006 · 86 citations
Pathogenesis of urinary tract infection: an update
AbstractPURPOSE OF REVIEW: Urinary tract infection is the second most common bacterial infection in children. It may cause renal scarring leading to secondary hypertension and chronic kidney disease. Recent information has greatly improved our understanding of the pathogenesis of urinary tract infection and renal scarring. RECENT FINDINGS: Urothelium, an anatomical barrier for innate immune responses, expresses toll-like receptors with the capacity to recognize pathogen-associated molecular patterns. Engagement of toll-like receptors can lead to uroepithelial cell activation and production of inflammatory mediators. These include complement proteins, other bactericidal peptides, cytokines, chemokines, defensins and adhesion molecules. The resulting inflammatory infiltrate serves to aid bacterial clearance but can also lead to renal damage. Furthermore, interactions between urinary proteins, such as Tamm-Horsfall protein, and TLR-4 add to the complexity of this defense system. Interindividual variability in cellular response may in part be responsible for variable clinical outcomes. Polymorphisms in a number of candidate genes in this host defense mechanism may be involved in determining those patients who are susceptible to recurrent infections and renal scarring following urinary tract infection. SUMMARY: Further understanding of the basic molecular mechanisms of urinary tract infection and translating these bench data to the bedside holds the promise of improving diagnosis and therapeutic strategies of treating urinary tract infection and preventing recurrence and renal scarring.
Expert Opinion on Drug Safety · 2015 · 4 citations
Dronedarone and renal impairment: evaluation of Spanish postmarketing reports and review of literature
AbstractBACKGROUND: Renal impairment associated with dronedarone use is hardly known. Our aim is to describe the characteristics of spontaneous reports involving renal adverse reactions with use of dronedarone. METHODS: In the Spanish Pharmacovigilance database, reports with renal reactions and dronedarone until May 2014 were retrieved and analyzed. Also, a review of case reports of renal failure and dronedarone was conducted in MEDLINE. RESULTS: Dronedarone was found as a suspected drug in 192 reports, 10 (5.2%) of these reports described renal reactions. Renal reactions appeared until 3 months after the onset of dronedarone treatment. In 5 out of 10 cases, dronedarone was withdrawn and the patient recovered. The Reporting Odds Ratio was 2.88 [95% CI 1.52 - 5.46; p < 0.05]. Additionally, eight cases were found in the medical literature. In five of them, the patient outcome was described as recovered. One patient had to undergo hemodialysis for the treatment of their renal impairment. CONCLUSIONS: The effect of dronedarone on the renal function is supported by limited information; therefore, the cases from spontaneous reporting system and those from the medical literature could give relevant additional information. Our analysis shows a potential relationship between dronedarone use and renal impairment. Further studies are needed to confirm these findings.
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.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
