DeCure's autonomous Nephrology AI scientist is researching a drug-repurposing hypothesis for nephrolithiasis — screening already-approved drugs against its 37-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleNephrolithiasis maps to a 37-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 nephrolithiasis 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
alanine--glyoxylate aminotransferase (AGXT) — AGXT 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 plpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5LUC · 1.8 Å · ligand PYRIDOXAL-5'-PHOSPHATE (PLP). Experimental structure, not a prediction.
What the evidence adds up to
A genome-wide search for linkage in a single Spanish kindred with 18 individuals identified a suggestive gene locus for autosomal dominant nephrolithiasis on chromosome 9q33.2–q34.2, with a two-point LOD score of 1.99 for marker D9S159 and a multipoint LOD score of 2.7 for markers D9S1881-D9S164. The locus, designated NPL1, was restricted to a 14 Mb interval by recombination events. The responsible gene has not been identified.
Treatment preferences for complex urinary calculi vary significantly by geography and training era. In a survey of Minnesota urologists (49% response rate), percutaneous nephrolithotomy for staghorn calculi was offered by 100% of metropolitan and urban urologists but only 57% of rural urologists. For a large lower-pole calculus with unfavourable anatomy, 82% of metropolitan urologists selected PCNL while 43% of rural urologists considered shockwave lithotripsy as initial therapy. Urologists trained after 1980 were more likely to offer PCNL (100% vs 81%) and ureteroscopy (16% vs 0%) than those trained before 1980.
Ceftriaxone, a third-generation cephalosporin, can induce nephrolithiasis as a rare side effect. The complication generally resolves spontaneously with cessation of the drug, though severe cases can cause post-renal acute renal failure. High doses and extended treatment periods are considered responsible, but there is limited information about the mechanism of development.
A 2024 review notes that the incidence of nephrolithiasis is increasing, that the etiology is unclear, stone composition complicated, and recurrence rate high after surgery. A 2025 review discusses pharmacotherapeutic strategies used in the Russian Federation and foreign practice but provides no efficacy data from controlled trials. What remains missing is identification of the responsible gene at the NPL1 locus, prospective data on whether practice pattern disparities affect patient outcomes, mechanistic understanding of ceftriaxone-induced stones, and any randomised trial evidence that any drug prevents recurrence or dissolves existing stones.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Mapping a new suggestive gene locus for autosomal dominant nephrolithiasis to chromosome 9q33.2–q34.2 by total genome search for linkage
AbstractBACKGROUND: Nephrolithiasis is a complex, multifactorial disease resulting from genetic and environmental interaction. The pathogenesis of nephrolithiasis is far from being understood. So far, no gene locus for autosomal dominant nephrolithiasis only has been described. We here identified a new suggestive gene locus for autosomal dominant nephrolithiasis by a genome-wide search for linkage in a Spanish kindred with nephrolithiasis. METHODS: Clinical data, blood and urine samples of 18 individuals from a Spanish kindred with nephrolithiasis were collected. We performed a genome-wide search for linkage using 380 polymorphic microsatellite markers. RESULTS: Nephrolithiasis segregated in this Spanish kindred in a pattern compatible with autosomal dominant inheritance. The total genome search yielded the highest two-point LOD score of Z(max) = 1.99 (theta = 0) for marker D9S159 on chromosome 9q33.2-q34.2. Multipoint analysis of 24 polymorphic markers used for further fine mapping resulted in a LOD score of Z(max) = 2.7 (theta = 0) for markers D9S1881-D9S164, thereby identifying a new gene locus for autosomal dominant nephrolithiasis (NPL1). Two recombination events define D9S1850 as the centromeric flanking marker and D9S1818 as the telomeric flanking marker, restricting the NPL1 locus to a 14 Mb interval. CONCLUSION: We here identified a new suggestive gene locus (NPL1) for autosomal dominant nephrolithiasis. It is localized on chromosome 9q33.2-q34.2. The identification of the responsible gene will provide new insights into the molecular basis of nephrolithiasis.
AbstractPURPOSE: To evaluate treatment preferences for complex urinary calculi. MATERIALS AND METHODS: A questionnaire was sent to 174 members of the Minnesota Urological Society. Three case scenarios were presented: a 1.5-cm lower-pole calculus with unfavorable anatomy, a 1.4-cm proximalureteral calculus, and a staghorn calculus. The treatment options offered were extracorporeal shockwave lithotripsy (SWL), ureteral stenting, ureteroscopy (URS), percutaneous nephrolithotomy (PCNL), and open surgery. RESULTS: Our survey response rate was 49%. A PCNL for staghorn calculi was more likely to be offered by urologists in metropolitan (100%; P<0.001) and urban (100%; P=0.003) settings than rural settings (57%). Whereas only 22% of urban and metropolitan urologists would offer anatrophic nephrolithotomy, 43% of rural urologists would include this among their treatment options. A PCNL was more likely to be offered by urologists trained after 1980 (100%) than by urologists trained before 1980 (81%; P=0.004). For a large lower-pole calculus with unfavorable anatomy, urologists with >50% managed-care practices were more likely (91%) than urologists with <50% managed-care practices (65%) to select PCNL for such stones (P=0.034). Whereas 82% of metropolitan urologists would select PCNL, 43% of rural urologists would consider SWL as initial therapy. A URS was more likely to be offered by urologists trained after 1980 (16%) than by urologists trained before 1980 (0; P=0.044). For a large proximal-ureteral calculus, metropolitan urologists were most likely (64%) to use stents initially (urban 28%; P=0.014; rural 14%; P=0.017). Rural urologists were more likely to offer SWL (100%) than were metro urologists (55%; P=0.024). CONCLUSIONS: Initial therapy for nephrolithiasis differs significantly according to geographic location, year of residency completion, and the percentage of managed-care patients in a urologist's practice. Future emphasis should be placed on increasing the availability of endoscopic techniques in rural settings.
Mini-Reviews in Medicinal Chemistry · 2016 · 7 citations
Research Progress of Mechanisms of Ceftriaxone Associated Nephrolithiasis
AbstractBACKGROUND: Urinary calculi can be caused by a variety of reasons, such as metabolic abnormalities, urinary tract infection and obstruction. Certain medications can induce urinary stone disease. Ceftriaxone, a third generation cephalosporin with broad spectrum antibiotic activity, primarily eliminated by the kidneys, has now been widely used for treatment of infection. It has been long considered safe, especially in children. However, more and more cases about ceftriaxone induced nephrolithiasis as a rare side effect have been reported. CONCLUSION: This complication generally resolves spontaneously with cessation of the drug. Severe nephrolithiasis can cause post renal acute renal failure (PARF). There is limited information about how this complication develops, though high doses and extended treatment periods are generally considered to be responsible. Understanding the mechanisms would help the doctors to be aware of this rare complication and respond with proper treatment. The primary goal of this review is to discuss the possible mechanisms based on the most recent literatures.
Discovery Medicine · 2024 · 3 citations · open access
Herbo-Mineral Medicine, Lithom Exhibits Anti-Nephrolithiasis Activity in Rat Model of Hyperoxaluria by Attenuating Calcium Oxalate Crystal Formation and Oxidative Stress
AbstractBackground: Calcium oxalate monohydrate (COM) forms the most common type of kidney stones observed in clinics, elevated levels of urinary oxalate being the principal risk factor for such an etiology. The objective of the present study was to evaluate the anti-nephrolithiatic effect of herbo-mineral formulation, Lithom. Methods: The <i>in vitro</i> biochemical synthesis of COM crystals in the presence of Lithom was performed and observations were made by microscopy and Scanning Electron Microscope (SEM) based analysis for the detection of crystal size and morphology. The phytochemical composition of Lithom was evaluated by Ultra-High-Performance Liquid Chromatography (UHPLC). The <i>in vivo</i> model of Ethylene glycol-induced hyperoxaluria in Sprague-Dawley rats was used for the evaluation of Lithom. The animals were randomly allocated to 5 different groups namely Normal control, Disease control (ethylene glycol (EG), 0.75%, 28 days), Allopurinol (50 mg/kg, <i>q.d.</i>), Lithom (43 mg/kg, <i>b.i.d.</i>), and Lithom (129 mg/kg, <i>b.i.d.</i>). Analysis of crystalluria, oxalate, and citrate levels, oxidative stress parameters (malondialdehyde (MDA), catalase, myeloperoxidase (MPO)), and histopathology by hematoxylin and eosin (H&E) and Von Kossa staining was performed for evaluation of Lithom. Results: The presence of Lithom during COM crystals synthesis significantly reduced the average crystal area, feret's diameter, and area-perimeter ratio, in a dose-dependent manner. SEM analysis revealed that COM crystals synthesized in the presence of 100 and 300 μg/mL of Lithom exhibited a veritable morphological transition from irregular polygons with sharp edges to smoothened smaller cuboid polygons. UHPLC analysis of Lithom revealed the presence of Trigonelline, Bergenin, Xanthosine, Adenosine, Bohoervinone B, Vanillic acid, and Ellagic acid as key phytoconstituents. In EG-induced SD rats, the Lithom-treated group showed a decrease in elevated urinary oxalate levels, oxidative stress, and renal inflammation. Von Kossa staining of kidney tissue also exhibited a marked reduction in crystal depositions in Lithom-treated groups. Conclusion: Taken together, Lithom could be a potential clinical-therapeutic alternative for management of nephrolithiasis.
Research Progress of Drugs in Prevention and Treatment of Nephrolithiasis.
AbstractWith the improvement of people's living standards,the incidence of nephrolithiasis is increasing year by year.Nephrolithiasis poses a serious threat to the patients due to the unclear etiology,complicated composition of stones,and high recurrence rate after surgery.As the research on the pathogenesis and pathophysiology of nephrolithiasis keeps deepening in recent years,researchers have made achievements in the drug treatment,which has become a hot topic for urologists.This paper reviews the advances in the research on the possible formation mechanism and drug-induced litholysis and prevention for nephrolithiasis,aiming to provide theoretical references for subsequent clinical research.
Pharmacotherapeutic strategies for the treatment of urolithiasis
AbstractThe aim of the review is to examine the evidence on models and strategies for pharmacotherapy of urolithiasis and new treatment methods. This article discusses the main medicinal products used for the pharmacotherapy of nephrolithiasis in the Russian Federation in accordance with the clinical recommendations of the Russian Society of Urologists, as well as those used in foreign practice.
Egyptian Journal of Rabbit Science · 2020 · 0 citations · open access
THERAPEUTIC POTENTIAL OF Citrus aurantium ON UROLITHIASIS INDUCED BY ETHYLENE GLYCOL IN MALE RABBITS
AbstractNephrolithiasis is a complex physicochemical event which starts with urinary supersaturation and then leads to aggregation of renal crystal forming constituents within the kidneys.Researches gives much attention for better medical therapy and assess a satisfactory drug to prevent renal stone formation. The purpose of the study was to detect the effectiveness of Citrus aurantium (bitter orange) juice on ethylene glycol induced nephrolithiasis in male rabbits. Animals were divided into five groups (n=8) in which group 1 as control (C), group 2 as ethylene glycol non treated group (EG), group 3 as ethylene glycol group treated with bitter orange juice (EG+B.O), group 4 as ethylene glycol group treated with Citraforte (EG+C) and group 5 as ethylene glycol group treated with bitter orange juiceand Citraforte (EG+B.O+C).Ethylene glycol was givento group 2-5 in drinking water for 21st days for the induction of kidney stones then the treatments were continued for successive 3 weeks. The obtained results showed a significant increase(p≤0.05) in the serum level of total protein, albumin, phosphorus, uric acid, creatinine, blood urea nitrogen BUN,Malondialdehyde (MDA) and a significant decrease in calcium, catalase (CAT), Superoxidase dismutase(SOD) and glutathione (GSH) in the group of rabbits treated with ethylene glycol.All the estimated parameters showed an improvement in their values in the treated groups especially in group 5 which treated with bitter orange juice plus Citra forte. There was a detectable pathological lesion in the kidney tissues of rabbits in ethylene glycol group which improved with treatment by bitter orange juice and or Citraforte. In conclusion:Co-administration of bitter orange (Citrus aurantium) juice with Citraforte initiated a synergistic action for curing urolithiasis induced by ethylene glycol in male rabbits.
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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