DeCure's autonomous Nephrology AI scientist is researching a drug-repurposing hypothesis for nephrotic syndrome, type 3 — 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, type 3 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, type 3 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
In a 2015 single-centre prospective study, 72 children with steroid-sensitive but frequently relapsing or steroid-dependent nephrotic syndrome were given either mycophenolate mofetil (MMF, 20–30 mg/kg/day, n = 34) or tacrolimus (TAC, 0.05–0.15 mg/kg/day, n = 38) for 12 months, both combined with low-dose steroids. In the MMF group, mean 6-month relapse rates fell from 2.56 episodes before therapy to 0.76 in the first 6 months and 0.67 in the next 6 months. In the TAC group, rates fell from 2.39 to 0.41 and then 0.42. No significant difference in relapse rate was found between the groups at any time point, and cumulative sustained remission and adverse event incidence were also similar. The authors concluded that MMF and TAC showed similar efficacy in maintaining remission in this population.
A 2024 retrospective multicentre cohort study reviewed 121 children with idiopathic nephrotic syndrome (median age at diagnosis 4.5 years, median follow-up 3.7 years) to identify factors predicting the need for steroid-sparing agents after a diagnosis of frequent relapses or steroid-dependent nephrotic syndrome. The only significant predictor was time to subsequent relapse after that diagnosis, using a 3-month threshold (adjusted hazard ratio 2.26, 95% CI 1.26–4.05). Children who relapsed within 3 months required steroid-sparing agents earlier (log-rank p = 0.005), had more relapses, more steroid-related adverse events, and were more likely to become steroid-dependent. The authors called for further prospective research to confirm this.
A 2007 review of complications in childhood nephrotic syndrome noted that untreated disease can cause infections, hypovolaemia, hypercoagulability, hyperlipidaemia, anaemia, and growth and development delays. It stated that morbidity and occasional mortality arise from inadequate management and complications, not from renal failure, and emphasised the need for clinical judgement and family cooperation.
A 2019 case report described a 52-year-old man with Waldenström’s macroglobulinaemia who presented with nephrotic syndrome, minimal change disease, capillary pseudothrombi, and chronic kidney disease. Treatment directed at the macroglobulinaemia with bortezomib, thalidomide, and dexamethasone lowered serum IgM and improved proteinuria and serum creatinine. This single case does not provide controlled evidence for any drug in nephrotic syndrome type 3.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Nephrology · 2015 · 21 citations
Evaluation of mycophenolate mofetil or tacrolimus in children with steroid sensitive but frequently relapsing or steroid‐dependent nephrotic syndrome
AbstractAIM: Approximately 30-40% of children with steroid sensitive nephrotic syndrome have frequently relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS). Mycophenolate mofetil (MMF) and tacrolimus (TAC) are often alternative treatment choices for these patients. METHODS: A single-center prospective study was conducted to compare the efficacy of MMF or TAC in reducing relapses and maintaining remission in children with FRNS or SDNS. Of the 72 recruited patients, either MMF (20∼30 mg/kg/d, n = 34) or TAC (0.05∼0.15 mg/kg/d, n = 38) was administered for 12 months. RESULTS: The mean 6-month relapse rates decreased from 2.56 episodes before therapy to 0.76 episodes in the first 6 months after therapy (c(2) = 44.362, p < 0.001) and 0.67 in the next 6 months (c(2) = 37.817, p < 0.001) in the MMF group. In the TAC group, the mean 6-month relapse rates decreased from 2.39 episodes before therapy to 0.41 episodes in the first 6 months after therapy (c(2) = 62.242, p < 0.001) and 0.42 in next 6 months (c(2) = 67.482, p < 0.001). No significant difference in the relapse rate was found between the groups (before therapy, c(2) = 0.902, p = 0.637; first 6 months, c(2) = 5.358, p = 0.147; second 6 months, c(2) = 4.089, p = 0.252). And there was also no significant difference in cumulative sustained remission and the incidence of adverse events between two groups. CONCLUSIONS: In combination with low-dose steroids, MMF or TAC presented similar efficacy in maintaining remission in children with FRNS/SDNS in the present study. Therapy with MMF or TAC is a promising strategy with a moderate risk of side effects in children who are steroid sensitive but have FRNS/SDNS.
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.
World Journal of Clinical Cases · 2019 · 4 citations · open access
Pseudothrombus deposition accompanied with minimal change nephrotic syndrome and chronic kidney disease in a patient with Waldenström's macroglobulinemia: A case report
AbstractBACKGROUND: Waldenström's macroglobulinemia (WM) is a rare lymphoid neoplasia, which can have renal complications. These rarely occur, and most common renal manifestations are mild proteinuria and microscopic hematuria. Herein we describe a case of WM that presented with pseudothrombi depositing in capillaries associated with minimal change nephrotic syndrome and chronic kidney disease (CKD). CASE SUMMARY: A 52-year-old man presented with features suggesting nephrotic syndrome. Extensive workups were done, and there were elevated serum levels of interleukin-6 and vascular endothelial growth factor (VEGF), capillary pseudothrombus accumulation associated with minimal change nephrotic syndrome, CKD, and WM. Treatment was directed at the patient's WM with bortezomib, thalidomide, and dexamethasone whereby serum immunoglobulin M (IgM) decreased. The damage of IgM on the kidney was corrected; thus, the patient's proteinuria and serum creatinine had improved. The patient is still under clinical follow-up. CONCLUSION: It is essential for clinicians to promptly pay more attention to patients presenting with features of nephrotic syndrome and do extensive workups to come up with a proper therapy strategy.
Dasatinib Induced Reversible Nephrotic Range Proteinuria Occurs More Frequently Compared to Other Tyrosine Kinase Inhibitors in the Treatment of Chronic Myeloid Leukemia
AbstractAbstract Introduction: Dasatinib is an oral inhibitor of Abl and Src family of kinases. Dasatinib can cause a pleural effusion in 14% to 30% of patients as well as pulmonary arterial hypertension. Its mechanism is not fully elucidated although vascular endothelial growth factor (VEGF)-mediated mechanism has been proposed. In the literature, there are sporadic case reports of dasatinib-induced proteinuria/nephrotic syndrome. It is also suggested that dasatinib-induced kidney injury involves the interruption of VEGF signaling pathway. In the present study, we present a series of 6 patients, who developed nephrotic-range proteinuria while on dasatinib therapy that resolved after switch to other TKIs or discontinuation. Also, we have analyzed the risk of TKI-associated proteinuria according to the TKI subtype in 256 CML patients having available results of urine protein level. Patients and Methods: A total of 256 patients with CML on TKIs, with available urine testing were reviewed. TKI therapy was as follows: Imatinib (n=147), dasatinib (n=67), nilotinib (n=13), ponatinib (n=13) and bosutinib (n=16). First, we have reviwed spot urinalysis result for proteinuria screening, and further reviewed in detail the result of 24-hour urine protein measurement. If proteinuria is detected, we had in-depth chart review on the case to exclude other causes of proteinuria such as diabetes, renal failure, urinary tract infecion or urinary tract malignancies, etc. After excluding other causes of proteinuria, we have calculated the incidence rate of proteinuria using 1,000 person-year considering duration of exposure to TKI therapy. Results: With median duration of 35 months of dasatinib therapy, 6 patients (8.9%) developed nephrotic range proteinuria, after excluding other secondary causes of proteinuria. All received dasatinib as 2nd line following Imatinib front line therapy. Out of 6 patients with proteinuria, 4 patients developed pleural effusion prior to the development of proteinuria. All of them showed optimal molecular response to dasatinib therapy at the time of proteinuria development including MR4.5 (n=4), MR4.0 (n=1) or MMR (n=1). One patient underwent renal biopsy which showed chronic glomerular endothelial cell injury and thin basement membrane nephropathy, consistent with finding of minimal change disease. All 6 cases had discontinued (n=3) or switched to other TKI therapy (imatinib n=1; botutinib n=1; nilotinib n=1) with complete resolution of proteinuria. In the 3 patients who had MR4.5 or deeper response when dasatinib was discontinued due to proteinuria, one lost MMR after 3 months, one maintained MMR (+13 months), and another without losing undetectable transcript level (+21 months). The incidence rate of TKI-associated proteinuria was analyzed according to the TKI subtype in 256 CML patients. Median follow-up duration was 31 months for 35 months for dasatinib (1-105 months), imatinib (1-172 months), 27 months for nilotinib (1-63 months), 5 months for bosutinib (1-22 months), and 1 month for ponatinib (1-14 months), respectively. The exposure year was 201.8 years in dasatinib (n=67), 523.2 years in imatinib (n=147), 31.4 years in nilotinib (n=13), 6.1 years in bosutinib (n=16) and 1.4 years in ponatinib (n=13). The incidence rate of proteinuria in dasatinib treated group was calculated as 29/1,000 person-year, while it was 0 in imatinib, nilotinib, bosutinib, ponatinib-treated group, respectively due to no case confirmed to have proteinuria after excluding secondary causes of proteinuria (Fisher's exact test p Conclusion: Development of nephrotic range proteinuria can be a toxicity from dasatinib therapy in CML treatment. Incidence rate is unexpectedly high at 29/1,000 person-year while there are no cases of nephrotic range proteinuria with exposure to other TKIs. All the proteinuria events were reversed completely after discontinuation/switch of dasatinib. Medical attention is to be paid for this unusual toxicity related to dasatinib therapy. Further study is strongly warranted to reach a clear conclusion for the incidence of this toxicity in a larger cohort. Disclosures Kim: BMS: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Paladin: Consultancy; Pfizer: Consultancy.
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.
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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