DeCure's autonomous Nephrology AI scientist is researching a drug-repurposing hypothesis for renal hypomagnesemia 2 — 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 moduleRenal hypomagnesemia 2 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 renal hypomagnesemia 2 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
FXYD domain containing ion transport regulator 2 (FXYD2) — FXYD2 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 y01drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7E20 · 2.7 Å · ligand CHOLESTEROL HEMISUCCINATE (Y01). Experimental structure, not a prediction.
What the evidence adds up to
Magnesium is involved in a wide spectrum of vital functions, but hypomagnesemia is under-recognised in clinical practice. In a 1990 study of 116 renal transplant patients, 24% (17 of 70) of those treated with cyclosporin were hypomagnesaemic, and all cases involved a renal magnesium leak that did not correlate with plasma bicarbonate, urate, calcium, cyclosporin or creatinine concentrations, nor with loop diuretic use or transplant duration. No azathioprine-treated patients (0 of 46) were hypomagnesaemic. Several antineoplastic agents have been linked to chronic hypomagnesemia, including anti-epidermal growth factor receptor agents such as cetuximab and panitumumab, cyclosporine, and the platinum-based agents cisplatin and carboplatin. A 2017 case report describes a middle-aged woman with head and neck cancer who sustained carboplatin-induced renal tubular damage, with a fractional excretion of magnesium of 16% consistent with renal wasting, making her relatively resistant to magnesium supplementation.
SGLT2 inhibitors have demonstrated a class effect in improving serum magnesium levels in patients with diabetes. A 2023 report of 4 cases of severe and refractory hypomagnesemia in patients without diabetes showed dramatic improvement after initiating SGLT2 inhibitors. Case 1 had calcineurin inhibitor-associated severe hypomagnesemia and was able to withdraw from high-dose oral magnesium supplementation. Cases 2 and 3 had refractory hypomagnesemia associated with platinum-based chemotherapy and achieved independence from intravenous magnesium supplementation, while case 4 had decreased intravenous magnesium requirements. Withdrawal of SGLT2 inhibitors in case 4 resulted in worsening serum magnesium levels and intravenous magnesium requirements. A 2025 multicenter retrospective case series from two U.S. medical centres described five patients with refractory hypomagnesemia who experienced significant improvement following initiation of SGLT2 inhibitors. Patients 1-4 showed marked renal magnesium wasting with severe symptomatic hypomagnesemia that responded robustly to SGLT2 inhibitor therapy. Patient 5 did not have renal magnesium wasting, but hypomagnesemia still improved. The addition of an SGLT2 inhibitor acutely improved hypomagnesemia in Patients 1 and 2 in an inpatient setting, and Patients 3-5 demonstrated sustained improvement across extended outpatient follow-up. All cases resulted in substantial reduction or cessation of magnesium supplementation.
Management strategies for drug-induced hypomagnesemia include magnesium supplementation and adjunctive therapies like amiloride and SGLT2 inhibitors to reduce renal magnesium losses. The 2025 review notes that hypomagnesemia is a frequent and often underrecognized electrolyte disturbance, especially in hospitalized and critically ill patients, arising from impaired intestinal absorption, renal magnesium wasting, and the effects of various medications including diuretics, antibiotics, antineoplastic agents, and immunosuppressants. The improvement of hypomagnesemia with SGLT2 inhibitors was irrespective of the diabetic status of the patient.
What is still missing are prospective controlled trials with adequate sample sizes to confirm the efficacy of SGLT2 inhibitors for renal hypomagnesemia 2 specifically, rather than for acquired hypomagnesemia from drugs or chemotherapy. The existing evidence is limited to case reports and small case series, with no randomised comparisons, no standardised dosing protocols, and no data on long-term safety or on which patients with genetic magnesium wasting would benefit most. Funding for such trials and better patient stratification by underlying magnesium-wasting mechanism are needed before any drug can be recommended for this rare disease.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
International Journal of Nephrology and Renovascular Disease · 2014 · 178 citations · open access
Hypomagnesemia: a clinical perspective
AbstractAlthough magnesium is involved in a wide spectrum of vital functions in normal human physiology, the significance of hypomagnesemia and necessity for its treatment are under-recognized and underappreciated in clinical practice. In the current review, we first present an overview of the clinical significance of hypomagnesemia and normal magnesium metabolism, with a focus on renal magnesium handling. Subsequently, we review the literature for both congenital and acquired hypomagnesemic conditions that affect the various steps in normal magnesium metabolism. Finally, we present an approach to the routine evaluation and suggested management of hypomagnesemia.
Kidney Medicine · 2023 · 25 citations · open access
SGLT2 Inhibitors in Management of Severe Hypomagnesemia in Patients Without Diabetes: A Report of 4 Cases
AbstractSodium/glucose cotransporter 2 (SGLT2) inhibitors have demonstrated a class effect in improving serum magnesium levels in patients with diabetes. Additionally, recent reports have shown their promising beneficial effects in the treatment of refractory hypomagnesemia in patients with diabetes. However, their role in treating hypomagnesemia in patients without diabetes remains unexplored. Here, we report 4 cases of severe and refractory hypomagnesemia that showed dramatic improvement after initiating SGLT2 inhibitors in patients without diabetes. Case 1 had calcineurin inhibitor-associated severe hypomagnesemia. Cases 2, 3, and 4 had refractory hypomagnesemia associated with platinum-based chemotherapy with or without gastrointestinal losses. Case 1 was able to withdraw from high-dose oral magnesium supplementation. Cases 2 and 3 achieved independence from intravenous magnesium supplementation, whereas case 4 had decreased intravenous magnesium requirements. All the cases demonstrated sustainably improved serum magnesium levels. Withdrawal of SGLT2 inhibitors in case 4 resulted in worsening serum magnesium levels and intravenous magnesium requirements. The extraglycemic benefit of this group of medications not only suggests the need for further studies to better understand the effect of SGLT2 inhibitors on magnesium homeostasis but also supports expanded use in a larger patient population.
Cyclosporin-Induced Renal Magnesium Leak in Renal Transplant Patients
AbstractRenal transplant patients (n = 116) attending an outpatients clinic were screened for hypomagnesaemia. No azathioprine-treated patients (n = 46) but 24% (17 of 70) of the cyclosporin treated patients were hypomagnesaemic. The hypomagnesaemia in all cases was associated with a renal magnesium leak. This leak did not correlate with plasma bicarbonate, urate, calcium, cyclosporin or creatinine concentrations, nor did it correlate with the use of loop diuretics or duration of the transplant. A renal magnesium leak is common in renal transplant patients treated with cyclosporin and it is independent of other markers of nephrotoxicity.
A case of chronic hypomagnesemia in a cancer survivor
AbstractOBJECTIVES: Hypomagnesemia is common among hospitalized patients, particularly those who are critically ill. It can be associated with a number of potentially life-threatening cardiovascular, neurological and behavioral manifestations. As opposed to acute, chronic hypomagnesemia is often underdiagnosed and underreported and as such may pose a diagnostic and therapeutic problem. CASE PRESENTATION: We describe a case of magnesium wasting in a middle-aged woman with head and neck cancer who presented with recurrent syncopal episodes complicated by a femur fracture 4 months after completing a course of carboplatin-containing chemotherapy. Fractional excretion of magnesium of 16% was consistent with renal wasting of magnesium. After ruling out all common causes of hypomagnesemia, it was concluded that she sustained carboplatin-induced renal tubular damage making her relatively resistant to magnesium supplementation. CONCLUSION: Several antineoplastic agents have been linked to chronic hypomagnesemia including anti-epidermal growth factor receptor agents such as cetuximab and panitumumab, cyclosporine, and the platinum-based agents cisplatin and carboplatin. The example case presented here illustrates the importance of chronic hypomagnesemia and its possible debilitating effects following carboplatin-containing chemotherapy. A growing numbers of cancer survivors are treated with these antineoplastic agents, and are hospitalized for non-cancer-related problems. These patients may have prolonged hypomagnesemia, and hence pose a diagnostic dilemma. We review the pathophysiology, etiology, diagnosis, clinical manifestations, monitoring and treatment of hypomagnesemia, with special attention to mechanisms of renal damage caused by platinum-containing chemotherapeutic agents.
The Clinical Spectrum of Acquired Hypomagnesemia: From Etiology to Therapeutic Approaches
AbstractHypomagnesemia is a frequent and often underrecognized electrolyte disturbance with important clinical consequences, especially in hospitalized and critically ill patients. This multifactorial condition arises from impaired intestinal absorption, renal magnesium wasting, and the effects of various medications. Magnesium, the second most abundant intracellular cation, is crucial in enzymatic and physiological processes; its deficiency is associated with neuromuscular, cardiovascular, and metabolic complications. This narrative review focuses on the mechanisms and clinical consequences of drug-induced hypomagnesemia, highlighting the major drug classes involved such as diuretics, antibiotics, antineoplastic agents, and immunosuppressants. Management strategies include magnesium supplementation and adjunctive therapies like amiloride and SGLT2 inhibitors to reduce renal magnesium losses. Recognizing and addressing drug-induced hypomagnesemia is essential to improve patient outcomes and prevent long-term complications.
Journal of Oncology Pharmacy Practice · 2012 · 1 citations
Isolated hypomagnesemia in a patient treated with capecitabine
AbstractHypomagnesemia is known to occur for a variety of renal, gastrointestinal and other causes, and is often associated with other electrolyte and metabolic disturbances. We present a case of isolated hypomagnesemia in a patient who had been treated with the chemotherapy agent capecitabine. The approach to diagnosis and treatment is discussed. We postulate that capecitabine may cause isolated hypomagnesemia, possibly due to renal magnesium loss.
Case Reports in Nephrology · 2025 · 0 citations · open access
SGLT2 Inhibitors as a Therapeutic Option for Both Acute and Chronic Refractory Hypomagnesemia in Diabetic and Nondiabetic Patients: A Multicenter Case Series
AbstractSodium-glucose cotransporter 2 (SGLT2) inhibitors are widely used in patients with kidney disease and have been shown to increase serum magnesium levels. Case reports have described their role in correcting hypomagnesemia; however, there is limited evidence regarding their efficacy in patients with renal magnesium wasting. Furthermore, data regarding their role in acute treatment and sustained efficacy to treat hypomagnesemia are lacking. We present a multicenter retrospective, observational case series from two U.S. medical centers describing five patients with refractory hypomagnesemia who experienced significant improvement following initiation of SGLT2 inhibitors. Patients 1-4 showed marked renal magnesium wasting with severe symptomatic hypomagnesemia which responded robustly to SGLT2 inhibitor therapy. Even though Patient 5 did not have renal magnesium wasting, hypomagnesemia still improved with the addition of an SGLT2 inhibitor. Furthermore, the addition of an SGLT2 inhibitor acutely improved the hypomagnesemia of Patients 1 and 2 in an inpatient setting, and Patients 3-5 demonstrated sustained improvement of hypomagnesemia across extended outpatient follow-up. The improvement of hypomagnesemia was irrespective of the diabetic status of the patient. All cases resulted in substantial reduction or cessation of magnesium (Mg) supplementation. These findings suggest a novel therapeutic application of SGLT2 inhibitors for managing intractable hypomagnesemia, both acutely and chronically, regardless of the diabetes being the primary culprit.
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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