DeCure's autonomous Nephrology AI scientist is researching a drug-repurposing hypothesis for pyelonephritis — screening already-approved drugs against its 14-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease modulePyelonephritis maps to a 14-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 pyelonephritis 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
cholinergic receptor nicotinic alpha 1 subunit (CHRNA1) — CHRNA1 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 clrdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9DMS · 1.92 Å · ligand CHOLESTEROL (CLR). Experimental structure, not a prediction.
What the evidence adds up to
In a study of 125 children with febrile urinary tract infections, acute pyelonephritis was significantly more likely in those with persistent fever before and after hospitalisation, elevated C-reactive protein, or positive renal ultrasound findings. E. coli strains carrying the papG II and iha genes were significantly more common in children who developed acute pyelonephritis. However, only host factors — fever for more than three days and C-reactive protein above 90.8 mg/l — were associated with subsequent renal scarring, not bacterial virulence factors. Age was not an independent predictor of acute pyelonephritis but did modify the effect of virulence factors.
A 2024 laboratory study tested how kidney-mimicking conditions affect the activity of three antibiotics against uropathogenic E. coli. The minimal inhibitory concentration of levofloxacin rose when pH was lowered and fell when pH was raised. The effects of sodium chloride and urea varied by bacterial strain and by antibiotic. The study tested only ertapenem, levofloxacin, and ceftriaxone, and the authors state that further research with additional antibiotics is needed.
A 2021 review summarises existing knowledge on uropathogen virulence, host innate and acquired immunity, and proteomic and genetic factors in acute pyelonephritis. It does not report new experimental data.
What is missing is a clinical trial that tests whether adjusting antibiotic choice or dose based on kidney pH or other physicochemical parameters improves outcomes in pyelonephritis. No study has yet stratified patients by host or bacterial factors to guide treatment and reduce renal scarring. Funding for such a trial, and a practical method for measuring kidney microenvironment parameters at the bedside, are not available.
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 · 2010 · 23 citations
Bacterial Virulence Factors are Associated With Occurrence of Acute Pyelonephritis but Not Renal Scarring
AbstractPURPOSE: We evaluated the influence of patient factors and virulence factors of uropathogenic Escherichia coli on the occurrence of acute pyelonephritis and subsequent renal parenchymal scarring. MATERIALS AND METHODS: We evaluated 80 boys and 45 girls 1 to 180 months old with febrile urinary tract infections who underwent renal scan to diagnose acute pyelonephritis and followup dimercapto-succinic acid scintigraphy at least 6 months later. Urinalysis, white blood cell count, uropathogenic E. coli genotype and vesicoureteral reflux were measured. Voiding cystourethrogram was investigated after acute pyelonephritis was confirmed by renal scan and acute inflammation subsided, about 2 to 4 weeks later. RESULTS: Acute pyelonephritis was significantly more likely to develop in children with urinary tract infections and persistent fever before and after hospitalization, elevated C-reactive protein or positive renal ultrasound findings. E. coli strains with the papG II and iha genes were significantly more likely to occur in patients with acute pyelonephritis. Patients with a fever for more than 3 days and C-reactive protein levels greater than 90.8 mg/l were significantly more likely to have renal scarring. Age was not an independent predictor of acute pyelonephritis, but modified the effect of virulence factors on the development of acute pyelonephritis. CONCLUSIONS: Bacterial virulence factors and host factors are associated with the occurrence of acute pyelonephritis. Host factors such as patient age and vesicoureteral reflux severity modify the influence of virulence factors, although only host factors are associated with the occurrence of renal scarring.
Acute pyelonephritis: risk factors, diagnosis and treatment
AbstractPyelonephritis is an acute urological condition that involves infection of one or both kidneys. The condition is not generally associated with high levels of mortality, but patients can become acutely ill and experience severe pain. Early recognition and treatment of pyelonephritis may limit morbidity. This article identifies patients at increased risk of pyelonephritis and discusses appropriate strategies to prevent serious complications.
European Urology Focus · 2024 · 3 citations · open access
Influence of Kidney Environment Parameters on Antibiotic Efficacy Against Uropathogenic Escherichia coli
AbstractBACKGROUND AND OBJECTIVE: Urinary tract infections (UTIs) are common infections affecting the urinary system, predominantly caused by bacterial pathogens, with Escherichia coli being the most frequent pathogen. Infections of the kidney (eg, pyelonephritis) are severe and challenging to treat, due to the specific tissue microenvironment. In this study, the influence of different parameters mimicking the kidney environment on the effectiveness of antibiotics prescribed for pyelonephritis on the growth of uropathogenic strains was analyzed. METHODS: To investigate the influence of different factors mimicking the kidney environment, we tested the effect of different kidney-representative concentrations of sodium chloride and urea, and different pH values on the efficacy of ertapenem, levofloxacin, and ceftriaxone. The effectiveness was assessed by determining the minimal inhibitory concentrations (MICs) against various E. coli strains. KEY FINDINGS AND LIMITATIONS: The study revealed that pH significantly influences the MIC values of levofloxacin. Acidification of the pH led to an increase of the MIC values, while an alkaline pH had the opposite effect. The influence of sodium chloride and urea concentrations was strain and antibiotic specific. Since three different antibiotics were tested in this study, further research with additional antibiotics is warranted. CONCLUSIONS AND CLINICAL IMPLICATIONS: These results suggest that the physicochemical conditions within the kidney can substantially influence the success of antibiotic therapy for pyelonephritis. Therefore, it is crucial for clinicians to consider these factors when selecting and dosing antibiotics. Further research is needed to evaluate a broader range of antibiotics and additional environmental parameters, to develop a more comprehensive understanding of how the kidney environment affects antimicrobial activity. This knowledge will be vital in optimizing treatment strategies for pyelonephritis, ultimately improving patient outcomes. PATIENT SUMMARY: The physicochemical conditions within the kidney influence the success of antibiotic therapy for pyelonephritis. Our findings are vital in optimizing treatment strategies and will ultimately improve patient outcomes.
Theoretical basis of the uropatogens interactions with the host-organism in case of occurrence and development of acute pyelonephritis (review – part III)
AbstractThe formation and development theories of bacterial inflammation in organs and tissues have been studied in detail and confirmed by experimental and clinical data. However, the development of inflammation in each organ has its characteristics associated with its structures and functions. This fully applies to acute pyelonephritis. The peculiar structure of uropathogens, their virulence, the reaction of the host organism in response to bacterial invasion, namely, factors of innate and acquired immunity, are analyzed in detail in the review. It reflects both the basic mechanisms of development of acute pyelonephritis and proteomic and genetic factors involved during inflammatory lesions.
The journal of the Japanese Practical Surgeon Society · 1995 · 0 citations · open access
A CASE OF EMPHYSEMATOUS PYELONEPHRITIS
AbstractEmphysematous pyelonephritis seen in a 54-year-old feamle is reported. The patient was seen at the hospital because of fever and left back pain. An about 15×10cm mass was palpated in her left flank. The patient was diagnsoed as left emphysematous pyelonephritis by plain abdominal X-ray films and abdominal CT scans. After derangements of blood glucose and electrolytes were corrected, an emergency nephrectomy was carried out. The patient recovered uneventfully after the operation. Emphysematous pyelonephritis is a fulminant necrotizing and suppurative inflammation. It is important to make an early diagnosis and to treat the lesion appropriately, since emphysematous pyelonephritis is sometimes lifethreatening.
Bulletin of the American Physical Society · 2010 · 0 citations
Using Image Processing to Determine Emphysema Severity
AbstractA 57-year-old man presenting with bilateral flank pain and hematuria was found to have severe bilateral emphysematous pyelonephritis. The patient was managed with a conservative approach consisting of systemic antimicrobials and decompression via percutaneous nephrostomy tubes with piperacillin-tazobactam instillations via nephrostomy and made a full recovery.
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.
