DeCure's autonomous Nephrology AI scientist is researching a drug-repurposing hypothesis for renal tubular acidosis — screening already-approved drugs against its 7-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleRenal tubular acidosis maps to a 7-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 tubular acidosis 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
carbonic anhydrase 1 (CA1) — CA1 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 phenylsulfonyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7Q0D · 1.24 Å · ligand methyl 4-chloranyl-2-(phenylsulfonyl)-5-sulfamoyl-benzoate (84Z). Experimental structure, not a prediction.
What the evidence adds up to
In type I renal tubular acidosis, nephrolithiasis is the main source of morbidity in adults and adolescents. A 1989 review of the condition identifies hypocitraturia as the most frequent risk factor for stone formation, present in both complete and incomplete forms of the disease. Hypercalciuria and alkaline urine are also major risk factors, and hyperuricosuria was found in 21 per cent of patients with type I renal tubular acidosis who had nephrolithiasis. The review notes that alkali therapy with bicarbonate or citrate salts increases citrate excretion in both complete and incomplete type I renal tubular acidosis, and that potassium citrate appears to reduce calcium excretion in hypercalciuric patients. A 1972 study of three patients with renal tubular acidosis found that citrate clearance was decreased during acidosis and remained low after acidosis was corrected, and that tubular reabsorption of citrate was increased regardless of the degree of acidosis.
A 2011 protocol for a prospective, multicentre, randomised controlled trial (the UBI Study) proposed to test whether correcting metabolic acidosis with sodium bicarbonate or another alkalinising agent such as sodium citrate reduces renal and cardiovascular mortality in patients with chronic kidney disease stages 3b and 4. The study planned to randomise 600 patients, 300 to a bicarbonate group aiming for serum bicarbonate above 24 mEq/L and 300 to usual treatment. The protocol was written because a 2007 Cochrane review had found no evidence that sodium bicarbonate corrected acidosis in pre-end-stage renal disease patients and concluded that randomised trials were needed to evaluate benefits and harms.
A 1980 review states that renal tubular acidosis is not a single entity, that differential diagnosis is straightforward, and that treatment is effective, but it does not specify which treatments or provide outcome data. The 1989 review notes that type I renal tubular acidosis can be hereditary, idiopathic, or secondary to autoimmune diseases such as Sjögren's syndrome and systemic lupus erythematosus, and that it occurs more frequently in women than men.
What is still missing is a completed randomised trial that tests alkali therapy specifically in patients with renal tubular acidosis and measures hard outcomes such as stone recurrence, kidney function decline, or mortality. The UBI Study was only a protocol; its results have not been reported here. No trial has stratified patients by the subtype of renal tubular acidosis or by the underlying cause (autoimmune, hereditary, idiopathic). Funding for such a trial, and for the long-term follow-up needed to detect differences in stone events or renal survival, remains absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
The Journal of Urology · 1989 · 93 citations
Nephrolithiasis in Renal Tubular Acidosis
AbstractRenal tubular acidosis is a term applied to several conditions in which metabolic acidosis is caused by specific defects in renal tubular hydrogen ion secretion. Three types of renal tubular acidosis generally are recognized based on the nature of the tubular defect. Nephrolithiasis occurs only in type I renal tubular acidosis, a condition marked by an abnormality in the generation and maintenance of a hydrogen ion gradient by the distal tubule. A forme fruste of type I renal tubular acidosis has been described in which the characteristic defect in distal hydrogen ion secretion occurs in the absence of metabolic acidosis (incomplete renal tubular acidosis). Type I renal tubular acidosis is a heterogeneous disorder that may be hereditary, idiopathic or secondary to a variety of conditions. Secondary type I renal tubular acidosis in sporadic cases is associated most commonly with autoimmune diseases, such as Sjögren's syndrome and systemic lupus erythematosus, and it occurs more frequently in women than men. Nephrolithiasis, which may occur in any of the subsets of type I renal tubular acidosis, accounts for most of the morbidity in adults and adolescents. Major risk factors for nephrolithiasis include alkaline urine, hypercalciuria and hypocitraturia. In addition, we found hyperuricosuria in 21 per cent of the patients with type I renal tubular acidosis with nephrolithiasis. The most frequently occurring risk factor, hypocitraturia, is due to decreased filtered load and/or to increased tubular reabsorption of filtered citrate. While increased tubular reabsorption may be due to systemic acidosis, hypocitraturia occurs in incomplete renal tubular acidosis. Furthermore, alkali therapy (either bicarbonate or citrate salts) increases citrate excretion in complete and incomplete type I renal tubular acidosis. These data suggest that hypocitraturia in type I renal tubular acidosis may be due to a defect in proximal tubule function. Hypercalciuria appears to have 2 causes. It may be due to metabolic acidosis, usually in children with a hereditary defect in urine acidification. In other cases familial idiopathic hypercalciuria causes nephrocalcinosis and nephrolithiasis resulting in distal tubular damage and type I renal tubular acidosis. In these latter cases hypercalciuria is present in complete and incomplete type I renal tubular acidosis. Potassium citrate appears to reduce calcium excretion in both types of hypercalciuric type I renal tubular acidosis.(ABSTRACT TRUNCATED AT 400 WORDS)
A prospective, multicenter, randomized, controlled study: the Correction of Metabolic Acidosis with Use of Bicarbonate in Chronic Renal Insufficiency (UBI) Study
AbstractBACKGROUND: A Cochrane Collaboration review (Roderick, Cochrane Data base of systemic reviews 2007, DOI 10.1002/14651858.CD0018.90.pub3) reported that there was no evidence for correction of acidosis by sodium bicarbonate in pre-end-stage renal disease (ESRD) patients, and concluded that randomized controlled trials (RCTs) are necessary to evaluate the benefits and harms of correcting metabolic acidosis in pre-ESRD patients. We wanted to evaluate if the administration of alcaly (mainly sodium bicarbonate) is able to significantly modify renal death and to reduce mortality due to cardiovascular events. METHODS: This is a proposal for a multicenter, prospective, cohort, randomized and controlled study. We will randomize 600 patients with chronic kidney disease (CKD) stages 3b and 4; 300 of these patients will be included in the bicarbonate study group (Bic), in which levels of bicarbonate should be kept >24 mEq/L; the other 300 patients will be included in the usual-treatment group (no-Bic). RESULTS: The aim of the research protocol is to demonstrate whether the optimal correction of uremic acidosis (with administration of sodium bicarbonate or of any other alkalinizing agent - e.g., sodium citrate) reduces renal and cardiovascular mortality. CONCLUSIONS: In conclusion, the Work Group on Conservative Therapy for Chronic Renal Insufficiency proposes this prospective, multicenter, cohort, randomized, controlled study to evaluate the effects of correction of acidosis on the progression of the kidney disease evaluated as renal death in ESRD patients.
AbstractRenal tubular acidosis is not one entity but several. Even though all its forms are characterized by the kidney's inability to excrete an appropriately acid urine, the mechanism of the defect, its laboratory and clinical manifestations, and its management vary considerably. One type can cause disabling complications in various organ systems, while another is generally asymptomatic. Differential diagnosis is straightforward, and treatment effective.
THE RENAL EXCRETION AND TUBULAR REABSORPTION OF CITRIC ACID IN RENAL TUBULAR ACIDOSIS
AbstractAbstract Three patients with renal tubular acidosis (RTA) have been examined during metabolic acidosis and after correction of the acidosis. Citrate (Ci) clearance was decreased in all patients during acidosis and was not normalized after correction of the acidosis. Renal metabolism of Ci was in the normal range except in one patient in whom the metabolism probably was decreased because of impaired renal function. Tubular reabsorption of Ci was increased independent of the degree of acidosis. We suggest this might be due to decreased tubular synthesis and secretion of Ci.
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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