DeCure's autonomous Nephrology AI scientist is researching a drug-repurposing hypothesis for nephrotic syndrome 16 — 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 moduleNephrotic syndrome 16 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
approvedSunitinibApproved drug
Structures already discussed alongside nephrotic syndrome 16 in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
KIT kinase domain — Sunitinib has a real, experimentally solved structure in complex with this target (PDB 3G0E, 1.6 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet b49drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3G0E · 1.6 Å · ligand Sunitinib (B49). Experimental structure, not a prediction.
What the evidence adds up to
A 2019 study identified compound-heterozygous mutations in NUP160 in a young girl with familial steroid-resistant nephrotic syndrome (SRNS) and focal segmental glomerulosclerosis (FSGS) who carried no mutations in other known SRNS genes. In a Drosophila nephrocyte model, silencing the fly NUP160 gene caused functional abnormalities, reduced cell size and nuclear volume, and disorganised nuclear membrane structure. Expression of wild-type human NUP160 completely rescued these defects, whereas the NUP160R1173× mutant allele failed entirely, and the NUP160E803K allele rescued only nuclear pore complex and nuclear lamin localisation defects. The authors concluded that NUP160 should be added to SRNS diagnostic gene panels.
In a 2008 study of 58 previously untreated adults with minimal-change nephrotic syndrome (MCNS) given alternate-day steroids, 54 patients (93%) achieved remission by 12 weeks and remained in remission at 16 weeks. Of those 54, 8 (14.8%) had frequent relapses and 9 (16.6%) had infrequent relapses. No serious steroid-related complications were reported. A 2007 review noted that untreated nephrotic syndrome in children can cause infections, hypovolaemia, hypercoagulability, hyperlipidaemia, anaemia, and growth delays, and that morbidity and occasional mortality arise from inadequate management and complications, not from renal failure itself.
A 2024 retrospective multicentre cohort study of 121 children with idiopathic nephrotic syndrome (median age at diagnosis 4.5 years, median follow-up 3.7 years) found that time to subsequent relapse after diagnosis of frequent relapses or steroid-dependent nephrotic syndrome (using a 3-month threshold) was the only significant predictor of needing a steroid-sparing agent (adjusted hazard ratio 2.26, 95% CI 1.26–4.05). Children who relapsed within 3 months of that diagnosis had a higher frequency of relapses, more steroid-related adverse events, and were more likely to develop steroid dependency. The authors called for prospective research to confirm this finding.
What remains missing is prospective validation of the NUP160 finding in larger patient cohorts, and confirmation that the timing-of-relapse predictor can be used to guide steroid-sparing therapy in a randomised trial. No trial has yet tested whether early introduction of steroid-sparing agents based on this predictor improves outcomes or reduces steroid toxicity.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of the American Society of Nephrology · 2019 · 49 citations · open access
Mutations in NUP160 Are Implicated in Steroid-Resistant Nephrotic Syndrome
AbstractSignificance Statement Mutations in >50 genes can lead to monogenic steroid-resistant nephrotic syndrome (SRNS). The authors found that a young patient with familial SRNS and FSGS carried novel compound-heterozygous mutations in NUP160 ; this gene encodes nucleoporin 160 kD, one of the protein components of the nuclear pore complex. Using an in vivo renal cell assay on the basis of Drosophila nephrocytes (an experimental podocyte model previously used to validate candidate renal disease genes and specific patient-derived mutant alleles), they validated the NUP160 gene variants as factors implicated in kidney pathology. The findings indicate that NUP160 should be included in the SRNS diagnostic gene panel to identify additional patients with SRNS carrying homozygous or compound-heterozygous NUP160 mutations. Background Studies have identified mutations in >50 genes that can lead to monogenic steroid-resistant nephrotic syndrome (SRNS). The NUP160 gene, which encodes one of the protein components of the nuclear pore complex nucleoporin 160 kD (Nup160), is expressed in both human and mouse kidney cells. Knockdown of NUP160 impairs mouse podocytes in cell culture. Recently, siblings with SRNS and proteinuria in a nonconsanguineous family were found to carry compound-heterozygous mutations in NUP160 . Methods We identified NUP160 mutations by whole-exome and Sanger sequencing of genomic DNA from a young girl with familial SRNS and FSGS who did not carry mutations in other genes known to be associated with SRNS. We performed in vivo functional validation studies on the NUP160 mutations using a Drosophila model. Results We identified two compound-heterozygous NUP160 mutations, NUP160R1173× and NUP160E803K . We showed that silencing of Drosophila NUP160 specifically in nephrocytes (fly renal cells) led to functional abnormalities, reduced cell size and nuclear volume, and disorganized nuclear membrane structure. These defects were completely rescued by expression of the wild-type human NUP160 gene in nephrocytes. By contrast, expression of the NUP160 mutant allele NUP160R1173× completely failed to rescue nephrocyte phenotypes, and mutant allele NUP160E803K rescued only nuclear pore complex and nuclear lamin localization defects. Conclusions Mutations in NUP160 are implicated in SRNS. Our findings indicate that NUP160 should be included in the SRNS diagnostic gene panel to identify additional patients with SRNS and homozygous or compound-heterozygous NUP160 mutations and further strengthen the evidence that NUP160 mutations can cause SRNS.
Minimal-Change Nephrotic Syndrome in Adults Treated with Alternate-Day Steroids
AbstractFifty-eight previously untreated adults with minimal-change nephrotic syndrome (MCNS), who had a mean follow-up period of 35.8 months, were studied with regard to their response to alternate-day steroid therapy. The nephrotic syndrome in 54 patients (93%) remitted by 12 weeks and patients continued to be in remission at 16 weeks. Of the 54 patients, 8 (14.8%) had frequent relapses and 9 (16.6%) had infrequent relapses. No serious complications as a result of steroid therapy were encountered.
Case Reports in Oncology · 2012 · 8 citations · open access
Development of a Nephrotic Syndrome in a Patient with Gastrointestinal Stromal Tumor during a Long-Time Treatment with Sunitinib
AbstractA patient with advanced gastrointestinal stromal tumor (GIST) receiving second-line treatment with sunitinib developed edema, increase of the serum creatinine, weight gain, nephrotic syndrome with proteinuria of 12 g/24 h, dyslipidemia, hypoalbuminemia and also presented with hypertension. A kidney biopsy showed an immunocomplex glomerulonephritis. Steroid treatment was started, but the clinical conditions and laboratory values did not improve. So in the hypothesis that the nephrotic syndrome was induced by sunitinib, sunitinib was temporarily discontinued with a subsequent reduction of proteinuria and improvement in blood pressure control. In the last years, the introduction of sunitinib has modified the natural history of advanced GIST. However, due to chronic and prolonged intake of this drug, there is increasingly frequent detection of late and unknown toxicities in clinical practice. In particular, the late renal toxicity from sunitinib may be the primary clinical problem with this drug in the case of prolonged treatment. Monitoring of kidney function and blood pressure should be performed for early detection of side effects such as hypertension and kidney dysfunction in advanced GIST patients receiving long-term treatment with sunitinib. A clinical collaboration between oncologists and nephrologists could be useful with the objective to optimize the management of sunitinib.
Immunosuppressive treatment of idiopathic membranous nephropathy: the dilemma continues
AbstractIdiopathic membranous nephropathy(IMN) is one of the most common causes of nephrotic syndrome (NS) in adults and may progress to end-stage renal disease(ESRD). Given the variable course, it remains unclear who to treat with immunosuppression(IS) and with what regimen. Corticosteroids, alkylating agents, calcineurin inhibitors (CNIs), and antimetabolities have all been used in randomized controlled trials (RCTs). Previous meta-analyses of these trials were unable to demonstrate a benefit on death or progression to ESRD compared to no treatment or placebo. Since the last round of these analyses (in 2004) additional RCTs have been published. The Cochrane Central Register of Controlled Trials and Medline were searched from 2003 until February 2012 for new RCTs in the treatment of IMN to update the database. Twelve trials were found. Due to significant heterogeneity of patients and regimens, they are discussed qualitatively only and are integrated with prior RCTs and relevant observational data. In conclusion, patients with non-nephrotic proteinuria should not be offered IS therapy. Those with NS and declining renal function should be treated. The best evidence supports a combined steroid and alkylating agent regimen. Calcineurin inhibitors clearly produce short-term benefit (proteinuria reduction and remission) but their ability to favorably affect death or ESRD remains unproven. There is little support for antimetabolite use. Other agents (rituximab and adrenocorticotropin) require further study. For the large group of patients with NS but normal renal function it remains a dilemma who to treat and with regimen.
AbstractNephrotic syndrome is an important chronic disease in children, characterized by minimal change disease in the majority. Untreated nephrotic syndrome may cause numerous complications, such as, infections, hypovolemia, hypercoagulability, hyperlipidemia, anemia, growth and development delays. The morbidity and occasional mortality is from inadequate management and complications and not due to renal failure. Expertise and clinical judgement as well as cooperation of the family are crucial for optimal management and a favorable outcome.
Timing of relapse as a key indicator of steroid-sparing requirements in childhood idiopathic nephrotic syndrome
AbstractBACKGROUND: Managing children with frequent relapses or steroid-dependent nephrotic syndrome poses challenges due to recurrent relapses necessitating prolonged steroid exposure, thus increasing susceptibility to long-term complications. Identifying those at risk of poor response to steroid therapy may be helpful to guide timely intervention with steroid-sparing agents. This study aimed to identify factors associated with steroid-sparing agent needs in children with frequent relapses or steroid-dependent nephrotic syndrome. METHODS: A retrospective multicenter cohort study was conducted by reviewing the medical records of children with idiopathic nephrotic syndrome treated between 2006 and 2023. Cox proportional regression analyzed prognostic factors for steroid-sparing agent requirements in children with frequent relapses or steroid-dependent nephrotic syndrome. The time-to-event analysis utilizing the Kaplan-Meier estimate examined the proportion of children needing steroid-sparing agents after diagnosis. RESULTS: Medical records of 121 children (85 males) diagnosed with idiopathic nephrotic syndrome at a median age of 4.5 years (range 1.3-12.8) were reviewed over a median follow-up of 3.7 years (range 1.0-15.0). Time to subsequent relapse post-frequent relapses or steroid-dependent nephrotic syndrome diagnosis (at 3-month threshold) emerged as the sole significant predictor of steroid-sparing agent requirement, adjusted hazard ratio (aHR) = 2.26, 95% confidence interval (CI) 1.26-4.05. Kaplan-Meier analysis indicated that an earlier first relapse (< 3 months) led to earlier steroid-sparing agent requirement (log-rank p = 0.005). Children who relapsed within 3 months post-frequent relapses or steroid-dependent nephrotic syndrome diagnosis exhibited a higher frequency of relapses, a greater incidence of steroid-related adverse events, and were more likely to develop steroid dependency. CONCLUSIONS: Early subsequent relapse following diagnosis of frequent relapses or steroid-dependent nephrotic syndrome was linked to earlier requirement of steroid-sparing agent therapy. Further prospective research is necessary to confirm this observation.
Serum neopterin levels in children with primary nephrotic syndrome
AbstractAbstract Aim: To assess the changes that occurs in serum neopterin levels in children with primary nephrotic syndrome. Methods: Serum neopterin levels were measured by ELISA in 38 children with active primary nephrotic syndrome (group I) and 17 children with primary nephrotic syndrome in remission (group II) and 20 healthy controls. All patients had normal creatinine clearance. Among group I, 28 patients were steroid‐sensitive while 10 patients were steroid‐resistant. Results: Serum neopterin levels were significantly elevated in group I patients (median = 30, 7.2–43.2 nmol/l) compared with group II (median = 6, 2–10 nmol/l, P <0.001) and controls (median = 3.2, range: 0.4–1.8 nmol/l, P <0.001). Group II patients had similar neopterin levels compared with controls ( P =0.71). There was a significant positive correlation between serum neopterin levels and the degree of proteinuria in group I patients (r = 0.4, P =0.01). No significant differences in serum neopterin levels were noted between steroid‐sensitive and steroid‐resistant patients ( P =0.4). Conclusion: Serum neopterin could be used as a marker of the activity of primary nephrotic syndrome but it could not be used to differentiate between steroid‐sensitive and steroid‐resistant patients.
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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