DeCure's autonomous Nephrology AI scientist is researching a drug-repurposing hypothesis for nephrocalcinosis — screening already-approved drugs against its 13-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleNephrocalcinosis maps to a 13-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 nephrocalcinosis 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
hypoxanthine phosphoribosyltransferase 1 (HPRT1) — HPRT1 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 3~{r},4~{r}drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5HIA · 1.773 Å · ligand [3-[(3~{R},4~{R})-3-(2-azanyl-6-oxidanylidene-1~{H}-purin-9-yl)-4-[(2~{S})-2-oxidanyl-2-phosphono-ethoxy]pyrrolidin-1-y
l]-3-oxidanylidene-propyl]phosphonic acid (YPG). Experimental structure, not a prediction.
What the evidence adds up to
In a cohort of 211 chronic kidney disease patients biopsied between 1989 and 2007, microscopic calcium phosphate deposition in the kidney was found in 4.6% of healthy kidney donors, 14.3% of patients with CKD stages 1–2, 20.2% of those with stages 3–4, and 54.0% of those with stage 5 or 5D. Lower estimated GFR, lower serum bicarbonate, and higher serum parathyroid hormone and calcium were independently associated with nephrocalcinosis. Serum phosphorus, but not nephrocalcinosis itself, predicted renal death regardless of renal function. In a separate prospective outpatient series from 2007–2013, 65 of 2695 patients (2.4%) received an imaging-based diagnosis of nephrocalcinosis. These patients were younger (median 37.7 vs 63 years), more often female (68% vs 51.4%), and had better preserved kidney function (median eGFR 103 vs 60 mL/min). Kidney stones were the most common reason for referral (35.4%), followed by electrolyte disturbances (22.7%). Autoimmune diseases were present in 29% and microcythaemia in 23%; among beta thalassaemic patients hypercalciuria was prominent.
Two 2024 reviews summarise recent risk factor discoveries for nephrocalcinosis. They list genetic mutations in CLCN5, CASR, and SLC34A3 as newly identified contributors, alongside metabolic, dietary, and environmental factors. The reviews emphasise advanced imaging for diagnosis and call for further research into genetic and environmental exposures, but provide no new clinical trial data or treatment outcomes.
No drug intervention is tested or proposed in any of these abstracts. The 2015 biopsy study shows that nephrocalcinosis is common in advanced CKD but does not independently predict renal death, while the outpatient series suggests it is often found in younger patients with preserved function and associated with autoimmune or haematological conditions. What remains missing are prospective trials that test whether correcting the associated metabolic disturbances—acidosis, hyperparathyroidism, hypercalciuria—alters the natural history of nephrocalcinosis, and whether genetic stratification could identify patients who might benefit from such interventions. No funding for such trials is reported.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Microscopic nephrocalcinosis in chronic kidney disease patients
AbstractBACKGROUND: Experimental data indicate that microscopic calcium phosphate deposition in the kidney (nephrocalcinosis) may accelerate progression of chronic kidney disease (CKD). Data on the prevalence, risk factors and implications of nephrocalcinosis in CKD patients are scarce. A mineral metabolism disorder could play an important pathogenetic role, as suggested by recent protocol biopsy findings in incident renal transplant recipients. METHODS: Kidney biopsy cylinders of CKD patients, collected between January 1989 and December 2007, were screened for the presence of nephrocalcinosis. Only patients with ≥1 parathyroid hormone (PTH) level available within 180 days of the biopsy were eligible for inclusion (n = 211). Demographics and mineral metabolism parameters were retrieved from medical files. Data on renal death (up to December 2012) were obtained from the Flemish ESRD registry. Baseline biopsies from 110 deceased kidney transplant donors served as controls. RESULTS: The prevalence of nephrocalcinosis in kidney donors and patients with CKD 1-2, CKD 3-4 and CKD 5-5D was 4.6, 14.3, 20.2 and 54.0%, respectively (P < 0.0001). Among CKD patients, patients with nephrocalcinosis were characterized by lower estimated GFR, lower serum bicarbonate level and higher serum PTH and calcium level. In multivariate regression analysis, high serum PTH, calcium and creatinine level, and low serum bicarbonate level were all significantly and independently associated with nephrocalcinosis. Serum phosphorus level, but not nephrocalcinosis predicted renal death, independent of renal function. CONCLUSIONS: Our data demonstrate that prevalence rates of nephrocalcinosis increase with increasing CKD stage to reach more than 50% in end-stage renal disease patients and suggest that acid-base and mineral metabolism disturbances are implicated in its pathogenesis.
Australian and New Zealand Journal of Medicine · 1992 · 5 citations
Late presentation and development of nephrocalcinosis in primary hyperoxaluria
AbstractA case of primary hyperoxaluria type 1 with complete deficiency of alanine:glyoxalate aminotransferase that first manifested at the age of 59 with irreversible acute on chronic renal failure is reported. Nephrocalcinosis, initially absent, developed rapidly after renal failure evolved. The possible role of hypovolaemia and contrast nephrotoxicity in precipitating the clinical onset is discussed. Primary hyperoxaluria should be considered in patients of any age presenting with unexplained renal failure, and appropriate systemic pathology of oxalosis.
Revisiting nephrocalcinosis: A single‐centre perspective. A northern <scp>I</scp>talian experience
AbstractAIM: Nephrocalcinosis is a clinical-pathological entity characterized by the deposition of calcium salts within the kidney parenchyma. Both the protean presentation and multiple causes may explain the lack of data regarding its prevalence. The aim of this study is to report the prevalence and main clinical features of nephrocalcinosis diagnosed in a newly opened nephrology outpatient unit. METHODS: Analysis on the data we prospectively gathered from the start of activity (2007-2013) was carried out. Clinical and laboratory data were collected from the medical records and from the general laboratory; diagnosis was based upon imaging data reviewed by the same radiologists. RESULTS: Sixty-five of 2695 patients referred to our unit were diagnosed with nephrocalcinosis (2.4%). The affected patients were younger than the overall out-patient population (median: 37.7 (min-max: 8-82) vs 63 years (2-102) P < 0.001), with higher female prevalence (68% vs 51.4%: P < 0.05) and better preserved kidney function (CKD-EPI 103 (23-165) vs 60 mL/min (3.2-169) P < 0.001). Kidney stones were the main reason for referral (35.4%), followed by electrolyte disturbances (22.7%), acute pyelonephritis (4.6%), AKI or CKD (4.6%). Nephrocalcinosis was associated with autoimmune diseases in 29% and with microcythaemia in 23%, while positive family history was present in 23% of patients. Various electrolyte disturbances were observed, with hypercalciuria being the hallmark of beta thalassaemic patients. CONCLUSIONS: Nephrocalcinosis is a rare, but not exceptional disease in nephrology. In Mediterranean countries, microcythaemia would appear to be a major cause of this disease. Greater awareness of nephrocalcinosis is needed for an integrated approach involving various branches of internal medicine and radiology.
NEPHROCALCINOSIS ASSOCIATED WITH HYPER-CHLORAEMIA AIND LOW PLASMA-BICARBONATE
AbstractJournal Article NEPHROCALCINOSIS ASSOCIATED WITH HYPER-CHLORAEMIA AIND LOW PLASMA-BICARBONATE Get access A. D. TELFORD GOVAN A. D. TELFORD GOVAN Research Department, Glasgow Royal Maternity and Women's Hospital Search for other works by this author on: Oxford Academic PubMed Google Scholar QJM: An International Journal of Medicine, Volume 19, Issue 4, October 1950, Pages 277–283, https://doi.org/10.1093/oxfordjournals.qjmed.a066561 Published: 01 October 1950 Article history Received: 25 January 1950 Published: 01 October 1950
Pediatria Polska · 2024 · 0 citations · open access
Nephrocalcinosis – latest reports on risk factors
AbstractThis review synthesizes recent discoveries in the risk factors of nephrocalcinosis, with a particular focus on novel findings.Nephrocalcinosis, characterized by the deposition of calcium salts in the renal parenchyma, is linked to a variety of genetic, metabolic, dietetic, and environmental factors.The study emphasizes the critical role of advanced imaging techniques in diagnosis and the identification of new genetic mutations in genes such as CLCN5, CASR, and SLC34A3 as significant factors contributing to the condition.The paper highlights the importance of recognizing these novel risk factors for better diagnosis, treatment, and prevention of nephrocalcinosis.It calls for further research to explore these new dimensions, particularly the genetic underpinnings and environmental exposures, to develop more effective management strategies and potentially prevent the onset of this complex renal condition.
Pediatria Polska · 2024 · 0 citations · open access
Nephrocalcinosis: the latest reports on risk factors – a review
AbstractThis review synthesizes recent discoveries in the risk factors of nephrocalcinosis, with a particular focus on novel findings. Nephrocalcinosis, characterized by the deposition of calcium salts in the renal parenchyma, is linked to a variety of genetic, metabolic, dietetic, and environmental factors. The study emphasizes the critical role of advanced imaging techniques in diagnosis and the identification of new genetic mutations in genes such as CLCN5, CASR , and SLC34A3 as significant factors contributing to the condition. The paper highlights the importance of recognizing these novel risk factors for better diagnosis, treatment, and prevention of nephrocalcinosis. It calls for further research to explore these new dimensions, particularly the genetic underpinnings and environmental exposures, to develop more effective management strategies and potentially prevent the onset of this complex renal condition.
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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