DeCure's autonomous Nephrology AI scientist is researching a drug-repurposing hypothesis for nephrosclerosis — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleNephrosclerosis maps to a 1-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 nephrosclerosis 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
polycystin 1, transient receptor potential channel interacting (PKD1) — PKD1 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 1rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8ZKH · 2.3 Å · ligand (1R)-2-{[(S)-{[(2S)-2,3-dihydroxypropyl]oxy}(hydroxy)phosphoryl]oxy}-1-[(hexadecanoyloxy)methyl]ethyl
(9Z)-octadec-9-enoate (PGW). Experimental structure, not a prediction.
What the evidence adds up to
A 2014 study of 1395 living kidney donors in the United States found that nephron hypertrophy (larger glomerular volume, larger tubular area, lower non-sclerotic glomerular density) and nephrosclerosis (higher globally sclerotic glomerular density) were distinct structural characteristics in normal adults. Male sex, higher urine albumin excretion, family history of end-stage renal disease, and higher body mass index were independently associated with nephron hypertrophy. Hypertension was not independently associated with nephron hypertrophy, but was independently associated with higher globally sclerotic glomerular density, along with older age.
A 2003 Norwegian retrospective study of 102 patients with biopsy-proven benign nephrosclerosis reported that 18% had developed end-stage renal failure and 24% had died within three years of biopsy; at 13 years the figures were 32% and 47%. Short-term predictors of end-stage renal failure were serum creatinine ≥200 µmol/l, systolic blood pressure ≥160 mmHg, and proteinuria ≥1 g/24h. Long-term predictors were increased serum creatinine and urinary protein. Independent risk factors for progression to end-stage renal failure were increased serum creatinine and increased urinary protein; independent risk factors for death were increased age and increased serum creatinine.
A 2007 perspective argued that the morphological findings of hypertensive nephrosclerosis may reflect complex environmental and genetic factors rather than a linear relationship with hypertension. A 2020 commentary noted that pathologic findings of nephrosclerosis can occur without hypertension, and that genome sequencing has identified mutations in Apolipoprotein L1, MYH9, and uromodulin genes as risk factors for non-diabetic chronic kidney disease. The authors stated that multiple studies have failed to prove or refute causality between benign hypertension and non-diabetic chronic kidney disease.
What remains missing is a prospective trial that stratifies patients by genetic risk variants (APOL1, MYH9, uromodulin) and tracks both blood pressure control and renal function decline over decades. Funding for such a trial is lacking, and the diagnostic category itself remains contested, making patient recruitment and standardisation of endpoints difficult.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Clinical Journal of the American Society of Nephrology · 2014 · 109 citations
Nephron Hypertrophy and Glomerulosclerosis and Their Association with Kidney Function and Risk Factors among Living Kidney Donors
AbstractBACKGROUND AND OBJECTIVES: The relationship of kidney function and CKD risk factors to structural changes in the renal parenchyma of normal adults is unclear. This study assessed whether nephron hypertrophy and nephrosclerosis had similar or different associations with kidney function and risk factors. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: From 1999 to 2009, 1395 living kidney donors had a core needle biopsy of their donated kidney during transplant surgery. The mean nonsclerotic glomerular volume and glomerular density (globally sclerotic and nonsclerotic) were estimated using the Weibel and Gomez stereologic methods. All tubules were counted in 1 cm(2) of cortex to determine a mean profile tubular area. Nephron hypertrophy was identified by larger glomerular volume, larger profile tubular area, and lower nonsclerotic glomerular density. Nephrosclerosis was identified by higher globally sclerotic glomerular density. RESULTS: The mean (± SD) age was 44 ± 12 years, 24-hour urine albumin excretion was 5 ± 7 mg, measured GFR was 103 ± 17 ml/min per 1.73 m(2), uric acid was 5.2 ± 1.4 mg/dl, and body mass index was 28 ± 5 kg/m(2). Of the study participants, 43% were men, 11% had hypertension, and 52% had a family history of ESRD. Larger glomerular volume, larger profile tubular area, and lower nonsclerotic glomerular density were correlated. Male sex, higher 24-hour urine albumin excretion, family history of ESRD, and higher body mass index were independently associated with each of these measures of nephron hypertrophy. Higher uric acid, higher GFR, and older age were also independently associated with some of these measures of nephron hypertrophy. Hypertension was not independently associated with measures of nephron hypertrophy. However, hypertension and older age were independently associated with higher globally sclerotic glomerular density. CONCLUSIONS: Nephron hypertrophy and nephrosclerosis are structural characteristics in normal adults that relate differently to clinical characteristics and may reflect kidney function and risk factors via separate but inter-related pathways.
Clinical prognostic factors in biopsy-proven benign nephrosclerosis
AbstractBACKGROUND: Hypertensive renal damage has become one of the most important causes of end-stage renal failure (ESRF) in Western countries. Affected patients rarely have a kidney biopsy and their diagnoses therefore remain uncertain. The objective of the present study was to examine patients suspected of renal glomerular disease, which at biopsy proved to have isolated benign nephrosclerosis. We wanted to study the effect of different clinical and laboratory variables at the time of biopsy on the short-term and long-term progression to ESRF and death. METHODS: We retrospectively examined 102 patients who were diagnosed by kidney biopsy in Norway between April 1988 and December 1990. All patients were followed by means of registries for approximately 13 years to describe renal and patient survival. RESULTS: The age of the patients at the time of biopsy was 55+/-15 years (range 15-88 years). Three years after the time of biopsy, 18% had developed ESRF and 24% had died; the corresponding numbers 13 years after biopsy were 32% and 47%. By Kaplan-Meier analyses, the following variables indicated short-term progression to ESRF: serum creatinine > or = 200 micro mol/l, systolic blood pressure > or = 160 mmHg and proteinuria > or = 1 g/24 h. In addition, patients with increased diastolic blood pressure, increased age and decreased serum albumin tended to develop ESRF more often. Long-term predictors of ESRF in Kaplan-Meier analyses were increased serum creatinine and urinary protein. Independent risk factors for progression to ESRF were increased serum creatinine and increased urinary protein. Independent risk factors for death were increased age and increased serum creatinine. CONCLUSIONS: Benign nephrosclerosis is a common condition that is associated with a high morbidity and mortality. Short-term predictors of ESRF differ from long-term predictors and this may reflect a pathophysiologically meaningful difference.
A perspective on arterionephrosclerosis: from pathology to potential pathogenesis
AbstractThe morphological findings of so-called hypertensive nephrosclerosis, rather than implying a linear direct relationship to damage induced by hypertension, may indicate complex environmental and genetic factors, which together foster the coexistence of renal lesion and hypertension in this clinical setting. We discuss the clinical and pathological criteria for diagnosis of arterionephrosclerosis, and possible pathogenetic factors, including hypertension, ethnicity, aberrant autoregulation, prothrombotic mechanisms, low birth weight, decreased nephron number, genetic factors and dysmetabolic syndrome.
Archives of Clinical and Medical Case Reports · 2020 · 0 citations · open access
In The Era of Precision Medicine- Where Does the Diagnosis “Hypertensive Kidney Disease” Fit?
AbstractHypertension has been labeled as a cause of non-diabetic chronic kidney disease for decades. In today’s era of precision medicine, labeling benign hypertension as the initial etiology for chronic kidney disease might not be accurate. We discuss an example of a 55-year-old African American patient with pathologic findings of nephrosclerosis without history of hypertension. The pathologic findings of nephrosclerosis can be as a result of obesity, aging, genetic susceptibility and variety of other previously undiagnosed primary renal disease, and hence shouldn’t automatically mark the diagnosis of hypertensive nephrosclerosis. Multiple studies to date have failed to prove or refute causality between benign hypertension and non-diabetic chronic kidney disease. Genome sequencing of non-diabetic kidney diseases have identified mutations in Apolipoprotein L1 gene, MYH9 gene and uromodulin gene as a risk factors for chronic kidney disease. There is no question that uncontrolled hypertension leads to progression of kidney disease, and hence blood pressure should be controlled adequately. The relationship between hypertension and kidney dysfunction should be viewed as an association and broad differential diagnoses should be pursued.
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.
