DeCure's autonomous Nephrology AI scientist is researching a drug-repurposing hypothesis for vesicoureteral reflux — screening already-approved drugs against its 9-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleVesicoureteral reflux maps to a 9-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 vesicoureteral reflux 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
5-hydroxytryptamine receptor 1B (HTR1B) — HTR1B 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 4-cyanophenyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6G79 · 3.78 Å · ligand 2-[5-[2-[4-(4-cyanophenyl)piperazin-1-yl]-2-oxidanylidene-ethoxy]-1~{H}-indol-3-yl]ethylazanium (EP5). Experimental structure, not a prediction.
What the evidence adds up to
A 1998 survey of 155 practising urologists found broad consensus on evaluating children after a first urinary tract infection (78.1% of respondents), using voiding cystourethrography and ultrasound at initial evaluation (99.4% and 96.8%), and screening siblings for reflux (83.2%). The survey identified persistent disagreement about when surgery is indicated and noted wide variation in postoperative hospital stay. The authors concluded that further clinical outcomes research was needed to resolve these controversies.
A 2007 cost-utility analysis using Markov models for grades II and III reflux compared five treatment algorithms from the perspective of parents and the medical institution. The protocol of no antibiotics and no follow-up imaging produced the best cost-utility. Sensitivity analysis showed that the utility penalties assigned to invasive imaging and outpatient pyelonephritis were the main drivers of which protocol ranked highest, with threshold values between -0.5 and -0.8. The authors stated that, given the lack of randomised trials, such models could guide current management.
Two small studies reported results for endoscopic injection of bulking agents. In 1997, Teflon paste was injected into 29 ureters of 18 children. Reflux was eliminated in 75.9%, decreased in 13.8%, and unchanged in 10.3%. Success was lower for high-grade reflux and abnormally shaped ureteral orifices. The authors noted that late recurrence could occur in a small proportion of cases. In 2018, a new bulking agent, polymethylmethacrylate/dextranomer, was injected into 33 renal refluxing units of 18 children (grades I–IV). At three months, reflux was corrected in 69.7%. One patient had urinary retention, and one had mild pyelectasis that resolved spontaneously. The authors called for long-term follow-up to confirm the material’s usefulness.
What remains missing are large, randomised trials comparing observation, antibiotics, and endoscopic or surgical intervention in clearly stratified patient groups. The existing evidence is limited to surveys, decision models, and small uncontrolled case series with short follow-up. Funding for such trials, standardised definitions of treatment success, and prospective tracking of long-term outcomes are still absent.
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 · 1998 · 27 citations
DISCUSSION: RESULTS OF A VESICOURETERAL REFLUX PRACTICE PATTERN SURVEY AMONG AMERICAN ACADEMY OF PEDIATRICS, SECTION ON PEDIATRIC UROLOGY MEMBERS
AbstractPURPOSE: We evaluated practice patterns among urologists managing vesicoureteral reflux, and identified areas of consensus and controversy requiring further research. MATERIALS AND METHODS: A 1-page questionnaire addressing various aspects of reflux management, including screening, diagnosis, treatment and followup, was mailed to a cohort of 225 practicing urologists identified by the membership roster of the American Academy of Pediatrics, Section on Pediatric Urology. Coded returned mailers were blindly analyzed and tabulated by 2 reviewers. Questionnaires were subdivided using a coding system by decade (1970s or earlier, 1980s and so forth) of participant membership in the American Urological Association. Select questions were analyzed to determine whether time of training affected the response. RESULTS: Of 225 surveys 155 were returned and usable (overall 60.8% response rate). General agreement exists regarding several important points in the management of vesicoureteral reflux, including evaluation of patients at the initial urinary tract infection (78.1% of respondents), use of voiding cystourethrography and ultrasound at the initial evaluation (99.4 and 96.8%, respectively), and evaluation of sibling reflux (83.2%). Certain absolute and relative indications for surgical intervention require further clarification. Various reimplantation techniques are used today, stents are not placed by the majority of practitioners and significant variations exist in the duration of postoperative hospital stay. CONCLUSIONS: Today there is substantial consensus among urologists on many issues regarding vesicoureteral reflux management. However, the areas of controversy will only be clarified by further scientific and clinical outcomes based research.
Cost-Utility Analysis of Treatment Algorithms for Moderate Grade Vesicoureteral Reflux Using Markov Models
AbstractPURPOSE: The optimal treatment algorithm for vesicoureteral reflux remains controversial. Previous decision analyses have attempted to determine the best approach solely from the cost or cure perspective but have not combined the goals of minimizing treatment and disease burden. We incorporated these considerations into a contemporary, comprehensive analysis of treatment for vesicoureteral reflux. MATERIALS AND METHODS: We examined costs from the perspective of the medical institution, and utility from the perspective of parents of children with grades II and III vesicoureteral reflux. Cost-utility analysis using Markov modeling was performed to ascertain which of 5 treatment algorithms best minimized morbidity and cost. A higher utility value was based on minimizing treatment and disease burden. Measures of treatment and disease burden included duration of suppressive antibiotics, number of invasive studies, pyelonephritis episodes, endoscopic treatments and open operations. All variables were varied spanning realistic ranges during sensitivity analyses to determine threshold values. RESULTS: The protocol of no antibiotics or followup imaging yielded the best cost-utility for vesicoureteral reflux grades II and III. Sensitivity analysis of variables spanning realistic ranges demonstrated that utility penalties for invasive imaging and outpatient pyelonephritis were particularly important in determining the highest utility protocols, with threshold values ranging from -0.5 to -0.8. CONCLUSIONS: In our models of treatment for vesicoureteral reflux a noninterventional approach constitutes the highest utility and least costly treatment for moderate grade reflux. Given the relative dearth of randomized trials, these analyses provide guidelines for current management of vesicoureteral reflux.
International Journal of Urology · 1997 · 10 citations · open access
Endoscopic Injection of Teflon for Correction of Primary Vesicoureteral Reflux in Children
AbstractBACKGROUND: Treatment of vesicoureteral reflux by endoscopic injection of Teflon paste has recently demonstrated a good success rate. This report describes our experience in treating vesicoureteral reflux in children with particular reference to follow-up data. METHODS: Between December 1993 and November 1994, endoscopic injection of Teflon paste into the submucosa was performed on 18 children (29 ureters) to correct vesicoureteral reflux. RESULTS: After treatment, reflux was eliminated in 75.9%, decreased in 13.8%, and unchanged in 10.3% of the ureters. The success rate was lower for high grade reflux cases and ureteral orifices with abnormal shapes. CONCLUSION: Long-term follow-up for up to 2 years demonstrated that although late recurrence may occur in a small proportion of cases, the procedure is safe, simple and effective for correcting vesicoureteral reflux.
Investigative and Clinical Urology · 2018 · 6 citations · open access
New bulking agent for the treatment of vesicoureteral reflux: Polymethylmethacrylate/dextranomer
AbstractPurpose: The aim of this study was to report preliminary results of endoscopic treatment of vesicoureteral reflux in children with a single injection of a new bulking agent, cross-linked dextran and polymethylmethacrylate mixture. Materials and Methods: We performed a single-center, single surgeon, prospective, off-label study using polymethylmethacrylate/dextranomer to treat vesicoureteral reflux. All patients underwent endoscopic injection, followed by renal ultrasound and voiding cystourethrogram at 3 months postoperatively to identify de novo or worsening hydronephrosis and vesicoureteral reflux correction (to Grade 0 or I). Results: Eighteen patients underwent injection of polymethylmethacrylate/dextranomer at our institution between April 2013 and December 2013. Ten were males and eight were females, with a median age of 58 months (range, 6 months to 5 years). Vesicoureteral reflux was unilateral in three patients and bilateral in 15, for a total of 33 renal refluxing units. Vesicoureteral reflux was Grade I in one renal refluxing unit, Grade II in 12, Grade III in 16, and Grade IV in four. Mean injected volume was 0.86 mL. Reflux was corrected in 23 renal refluxing units (69.7%) according to the 3-month voiding cystourethrogram. Complications included urinary retention in one patient. Mild pyelectasis was noted in one patient at 3 months, which spontaneously resolved 3 months later. Conclusions: Our short-term data show that polymethylmethacrylate/dextranomer injection can be used to treat vesicoureteral reflux with comparable efficacy to other substances currently used and a low rate of complications. Long-term follow-up is required to confirm the usefulness of this material in treating vesicoureteral reflux.
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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