DeCure's autonomous Nephrology AI scientist is researching a drug-repurposing hypothesis for renal hypoplasia — screening already-approved drugs against its 5-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleRenal hypoplasia maps to a 5-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 renal hypoplasia 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
lysine acetyltransferase 6B (KAT6B) — KAT6B 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6OIE · 2.075 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Renal hypoplasia is defined as a condition of arrested development in which the kidney remains below normal size or in an immature state. A 2020 pathology review describes three commonly recognised types — simple hypoplasia, oligomeganephronic hypoplasia, and segmental (Ask-Upmark) kidney — all sharing a reduction in the number of renal lobes. A fourth type, cortical hypoplasia, involves normal nephrogenesis but fewer nephron generations. The review examined 18 new cases and frames these entities within the broader concept of oligonephronia, a milder reduction in nephron mass linked to adult-onset hypertension and chronic kidney disease. No treatment or intervention is discussed in this paper.
A 2024 case report describes a 29-year-old man with chronic kidney disease secondary to renal hypoplasia who required kidney transplantation. He had been on peritoneal dialysis and presented with progressive deterioration, reduced functional capacity, fatigue, pulmonary congestion, and fluid retention, along with moderate to severe mitral regurgitation. The report focuses on anaesthetic management for the transplant surgery; no drug therapy for renal hypoplasia itself is mentioned.
A 2015 mouse model study shows that in normal kidney development, Sonic hedgehog (Shh) secreted from medullary collecting ducts establishes a gradient of Hedgehog signalling. The absence of Hedgehog signal, and thus the function of the GLI3 repressor, is critical for ureteric tip cell gene expression and nephron induction. In Ptc1−/−UB mice, which lack cortical GLI repressor, ureteric tip cell gene expression is impaired, resulting in reduced nephrogenesis and renal hypoplasia. This is a mechanistic study in mice, not a clinical trial.
No clinical trial data, drug efficacy results, or survival or response rates for any drug in renal hypoplasia are reported in these abstracts. What is still missing is any clinical trial testing a drug to increase nephron mass or slow progression, adequate patient stratification by hypoplasia subtype, and funding for such studies in humans.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Advances in Anatomic Pathology · 2020 · 30 citations · open access
Renal Hypoplasia, From Grossly Insufficient to Not Quite Enough: Consideration for Expanded Concepts Based Upon the Author’s Perspective With Historical Review
AbstractHypoplasia is defined in the Merriman-Webster dictionary as "a condition of arrested development in which an organ, or part, remains below the normal size, or in an immature state." The degree of reduced size is not definitional. Renal hypoplasia, however, has historically been defined as a more marked reduction in renal mass such that presentation in childhood is the norm. There are 3 commonly recognized types of renal hypoplasia, simple hypoplasia, oligomeganephronic hypoplasia (oligomeganephronia) and segmental hypoplasia (Ask-Upmark kidney). They have in common a reduction in the number of renal lobes. A fourth type, not widely recognized, is cortical hypoplasia where nephrogenesis is normal but there is a reduction in the number of nephron generations. Recently there has been great interest in milder degrees of reduced nephron mass, known as oligonephronia because of its association with risk of adult-onset hypertension and chronic kidney disease. Since the last pathology review of this topic was published by Jay Bernstein in 1968, an update of the renal pathology findings in renal hypoplasia is provided with a review of 18 new cases. The renal hypoplasias are then framed within the modern concept of oligonephronia, its diverse causes and prognostic implications.
Experimental and Clinical Transplantation · 2024 · 0 citations
Anesthetic Management for Kidney Transplant in a Young Patient With Mitral Regurgitation: Case Report.
AbstractPatients with chronic kidney disease who are candidates for transplant may experience changes in capillary permeability, coagulation, and the endocrine system; alterations in the pulmonary vasculature; and cardiac structural and functional changes. Patients with renal replacement by hemodialysis have a mortality rate 30 times higher than those who do not have uremia. According to the onset, duration, and severity of chronic kidney disease, cardiovascular disease will be reflected in baseline function and response to stress. For this reason, it is important to establish the functional condition so that preoperative management can be started and factors inherent to the patient and the surgical procedure can be modified. Here, we report a 29-year-old male patient with chronic kidney disease secondary to renal hypoplasia, with no family history. The patient had renal replacement therapy with peritoneal dialysis and had progressive deterioration of general status, decreased functional capacity, decreased tolerance to physical activity, presence of fatigue and pulmonary congestion, and retention of liquids, with a diagnosis of moderate to severe mitral regurgitation.
Model for HH signaling function in the ureteric epithelium.
Abstract<p>(A) During normal renal morphogenesis, <i>Shh</i> secreted from the medullary collecting ducts (purple) establishes a gradient of HH signaling resulting in distinct medullary GLI activator (blue) and cortical GLI repressor domains. While HH signaling activity has no functional requirement in the ureteric cell lineage, the absence of HH signal, and thereby function of GLI3 repressor is critical for ureteric tip cell-specific gene expression and subsequent nephron induction (B). In the absence of cortical GLI repressor, such as in <i>Ptc1<sup>−/−UB</sup></i> mice, ureteric tip cell-specific gene expression is impaired resulting in reduced nephrogenesis and renal hypoplasia.</p>
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.
