amiloride hydrochloride / Generic mfg. - LARVOL DELTA

The scaffold protein IQGAP1 regulates the epithelial Na+ channel. (PubMed, J Biol Chem) - "Functionally, co-expression of IQGAP1 with ENaC in Xenopus oocytes reduces ENaC surface abundance and amiloride-sensitive Na+ transport activity. Together, our data indicate that IQGAP1 binds to ENaC, which likely influences channel trafficking to regulate its cell surface abundance and Na+ transport function. More broadly, these observations suggest new physiological roles for IQGAP1 in Na+ and water absorption in epithelium."

Journal • IQGAP1

Management of neuropathic pain and paresthesia in patients with multiple sclerosis: A systematic review and network meta-analysis. (PubMed, Mult Scler Relat Disord) - "In managing MS-related neuropathic pain and paresthesia, a combination of pharmacological and non-pharmacological interventions may provide the best outcomes."

Journal • Retrospective data • Review • CNS Disorders • Multiple Sclerosis • Neuralgia • Pain

Data Analysis for Drug Repurposing for Effective Alzheimer's Medicines (DREAM)- Amiloride vs Triamterene (clinicaltrials.gov) - P=N/A | N=155963 | Completed | Sponsor: Brigham and Women's Hospital | Active, not recruiting ➔ Completed

Trial completion • Alzheimer's Disease • Cardiovascular • CNS Disorders • Hypertension

Mechanistic target of rapamycin complex-2 (mTORc2) mediates the effect of over-night high K+ on Kir4.1/Kir4.1 in the DCT and ENaC/ROMK in ASDN. (PubMed, Am J Physiol Renal Physiol) - "Amiloride-sensitive-Na+-currents (ENaC) were significantly lower in DCT2/CNT in Ks- RICTOR-KO mice than wild-type. In summary, mTORc2 plays a role in maintaining baseline-activity of Kir4.1/Kir5.1, ROMK and ENaC and it mediates the effect of overnight-HK on ENaC and ROMK in aldosterone-sensitive-distal nephron (ASDN). We conclude that mTORc2 plays a keyrole in stimulating renal K+ excretion during high-K+-loading by inhibiting Kir4.1/Kir5.1 in the DCT and stimulating ENaC and ROMK in ASDN."

Journal • RICTOR

PRL-3 enhances multiple myeloma cell survival in acidic microenvironments via metabolic adaptation and pH regulation. (ASH 2025) - "Pharmacologic inhibition of lactate and proton transport was performed using Syrosingopine (dualMCT inhibitor), AZD0095 (MCT4 inhibitor), AZD3965 (MCT1 inhibitor), Bafilomycin A1 (v-ATPase inhibitor),and ethyl isopropyl amiloride (EIPA; NHE1 inhibitor). Thissuggests compensatory roles among transporters and pathways whose importance varies depending onthe pH level. Increased metabolism and proton transport are associated with high PRL-3 expression,supporting PRL-3 as a key protein for cell survival in acidic conditions and a potential therapeutic targetin myeloma treatment."

Hematological Malignancies • Multiple Myeloma • ANXA5 • PTP4A3 • SLC16A1

Comparable One-Year Efficacy and Safety of Spironolactone Versus Amiloride in Resistant Hypertension: A Retrospective Cohort Analysis (AHA 2025) - "We matched for a total of 30 variables.ResultsPropensity-score matching generated two well-balanced cohorts (n = 414 each), with comparable age (mean 62.7 vs 63.8 years), sex distribution (54.3 % vs 56.5 % male), and comorbidities (Table 1). At 4 weeks, more amiloride-treated patients achieved SBP ≤ 130 mm Hg (53.6 % vs 44.2 %; RR 1.21, 95 % CI 1.05–1.40) and DBP ≤ 80 mm Hg (62.3 % vs 53.6 %; RR 1.16, 95 % CI 1.03–1.31), whereas by 52 weeks there were no differences in attainment of any blood-pressure target (SBP ≤ 130, SBP ≤ 140, DBP ≤ 80, DBP ≤ 90).There was no statistically significant difference between groups in all-cause mortality (13.3% vs 11.1%; RR 1.20, 95% CI 0.83–1.73), incidence of acute kidney injury (13.0% vs 15.2%; RR 0.86, 95% CI 0.61–1.20), or major adverse cardiovascular events (22.5% vs 23.7%; RR 0.95, 95% CI 0.74–1.22) at 52 weeks.ConclusionAmiloride and spironolactone had similar one-year AKI, MACE, all-cause mortality, and BP control."

Retrospective data • Acute Kidney Injury • Cardiovascular • Cerebral Hemorrhage • Hematological Disorders • Hypertension • Myocardial Infarction • Nephrology • Renal Disease

Hypomagnesaemia-associated hypokalaemia requires activation of both ENaC and ROMK. (PubMed, J Physiol) - "A lower natriuretic response to acute amiloride administration confirmed lower ENaC activity in mice on LM diet...We found that ENaC activity is lower following dietary Mg2+ restriction but is preserved with combined Mg2+/Na+ restriction, stimulating K+ secretion via ROMK. Our findings probably explain why Mg2+ restriction alone cannot cause hypokalaemia in vivo and provide new insights into the mechanisms of hypomagnesaemia-induced hypokalaemia."

Journal • Genetic Disorders

Phenotype and renal outcomes of patients with congenital arginine vasopressin-resistance. (PubMed, Nephrol Dial Transplant) - "Non-obstructive hydroureteronephrosis is a common complication of congenital AVP-R. CKD frequently develops in patients with phenotypically severe congenital AVP-R, independent of AVPR2 or AQP2 mutation."

Journal • Chronic Kidney Disease • Nephrology • Renal Disease

Bergeyella cardium variant induces a unique cytoplasmic vacuolization cell death floatptosis in macrophage. (PubMed, Cell Discov) - "Bacterial pathogens have evolved multiple mechanisms to modulate host cell death, evade host immunity, and establish persistent infection. SLC9A9 deficiency or amiloride administration increases host defense against BCV infection. These findings contribute to developing novel approaches to modulate cytoplasmic vacuolization cell death and treat infectious diseases."

Journal • Cardiovascular • Infectious Disease

Real-Time Chemical, Microbiological, and Physical Stability of Extemporaneously Compounded Amiloride Nasal Spray Over 90 Days at Refrigerated and Room Temperatures. (PubMed, Int J Pharm Compd) - "This was accomplished via a validated, high-performance liquid chromatography (HPLC) method at designated and appropriate time points to reveal that amiloride remained highly chemically stable over 50 days at 4 and 20 degrees Celsius and retained sufficient stability after 90 days from initial compounding. Additionally, the physical stability of the solution when combined with the preservative benzyl alcohol was confirmed via visual inspection, pH monitoring, and measuring of turbidity."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension • Mood Disorders • Psychiatry

New Mutations in Bartter Syndrome (BS) Type 1 (KIDNEY WEEK 2025) - "Case Description We describe a 22-year-old male with a history of severe hypokalemia managed with potassium supplements and amiloride who presented after routine labs revealed severe hypokalemia following missed doses of both medications...Prior genetic analyses were limited to sequential single-gene testing, an approach that was time-consuming, costly, and lacked complete diagnostic yield. This case illustrates the value of re-evaluating genetic testing in patients with previous inconclusive results to help identify novel mutations, as advances in technology now allow for the detection of mutations previously undetectable."

Metabolic Disorders • Nephrology • Rare Diseases

Ogilvie Syndrome and Abiraterone: Untangling Two Uncommon Causes of Refractory Hypokalemia (KIDNEY WEEK 2025) - "He was started on medication regimen of Amiloride, Eplerenone, and prednisone. This results in increased sensitivity to normal serum aldosterone levels and persistent, predominantly colonic, potassium wasting. This explains this patient’s improvement on aldosterone antagonists, as it worked to suppress expression of BK channels, as well as treatment of pseudo-obstruction."

Endocrine Disorders • Genito-urinary Cancer • Hypertension • Infectious Disease • Nephrology • Prostate Cancer • Renal Disease • Septic Shock • Solid Tumor

Renal Tubular Dysfunction as the Driving Force Behind Refractory Hypokalemia in Ogilvie Syndrome (KIDNEY WEEK 2025) - "This report details the case of a 57-year-old male with IgG kappa multiple myeloma undergoing treatment with daratumumab, lenalidomide, and dexamethasone (DRd) who developed severe Ogilvie's syndrome complicated by refractory hypokalemia (K ≤3.1 mEq/L despite aggressive IV repletion). The 48-hour lag between potassium normalization (Day 3) and colonic recovery (Day 5) demonstrates that electrolyte correction must precede functional GI improvement. Amiloride's effectiveness supports ENaC blockade as superior to mineralocorticoid antagonism in chemotherapy-induced tubular disorders."

Addiction (Opioid and Alcohol) • Endocrine Disorders • Hematological Malignancies • Metabolic Disorders • Multiple Myeloma • Nephrology • B2M

ASIC2 Assembles with Epithelial Sodium Channel (ENaC) Subunits to Form Mechanosensitive Channels (KIDNEY WEEK 2025) - "Conclusion Collectively, our findings suggest that ASIC2a assembles with ENaC β/γ subunits to form mechanosensitive channels. Future studies will examine whether the presence of ENaC β/γ subunits in the channel complex alter ion permeability or sensitivity to amiloride."

Liddle Syndrome: Clinical Phenotype and Therapeutic Response in a Novel Heterozygous SCNN1G Variant (KIDNEY WEEK 2025) - "Despite multiple antihypertensive medications (including spironolactone), over the years her blood pressure had remained elevated (range: 145/80-155/85 mmHg)...Treatment was modified to include amiloride (ENaC blocker), with discontinuation of potassium supplements...The patient was referred for genetic counseling for family planning afterward. Discussion This case highlights several important teaching points: (1) Liddle syndrome should be considered in patients with treatment-resistant hypertension and hypokalemia across all age groups; (2) SCNN1G variants, though less common, can present with classical Liddle syndrome features; (3) Clinical response to ENaC blockers may provide diagnostic confirmation when genetic findings are inconclusive; (4) Family screening is essential due to the autosomal dominant inheritance pattern; (5) Ongoing identification and functional characterization of novel ENaC variants is crucial, as expanding the spectrum of pathogenic variants..."

Clinical • Cardiovascular • Hypertension • Nephrology

A Case of Abiraterone-Induced Mineralocorticoid Excess Syndrome Associated with Rhabdomyolysis and Polyuria (KIDNEY WEEK 2025) - "After resuming prednisone and starting amiloride, his hyperkalemia resolved first, followed by gradual resolution of rhabdomyolysis and polyuria. Second, there has been historical reports of hypokalemia-associated tubular concentrating defects through disruption of AQP2 production. Despite treatment, both rhabdomyolysis and polyuria continued until successful normalization of serum potassium suggesting that the hypokalemia was the primary driver of our patient's presentation."

Clinical • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Hypertension • Prostate Cancer • Renal Disease • Solid Tumor

mTORc2 Stimulates Renal Potassium (K+) Excretion During Overnight-High-K+ by Simultaneously Stimulating Epithelial Sodium Channel (ENaC)/Potassium Kir1.1 Channel (ROMK) and Inhibiting Kir4.1/Kir5.1 (KIDNEY WEEK 2025) - "Funding NIDDK Support Background The mTORc2 is a multiprotein complex and RICTOR (rapamycin insensitive companion of mTOR) is one of the core components of mTORc2...In contrast, amiloride-sensitive Na + -currents (ENaC) and tertiapin-Q (TPNQ)-sensitive-K + -currents (ROMK) were lower in both late-DCT/early-connecting-tubule (CNT) and cortical- collecting-duct (CCD) of Ks-RICTOR-KO mice than Rictor flox/flox mice...It mediates the effect of high-K + -intake on ENaC and ROMK not only in the CCD but also in late-DCT/early-CNT. The mTORc2 plays a key role in stimulating renal K + excretion during high-K + -loading by simultaneously inhibiting Kir4.1/Kir5.1 and stimulating ENaC and ROMK."

RICTOR

Gain- and Loss-of-Function Variants in Epithelial Sodium (Na+) Channel Delta Subunit (KIDNEY WEEK 2025) - "Amiloride-sensitive currents (0.1 mM) representing ENaC activity were measured and compared within the same baches of oocytes expressing the WT or mutant channels...Conclusion Our results suggest that R297C is a gain-of-function low-frequency variant and G71S and C370R are loss-of-function rare variants of δENaC. These and other δENaC variants may contribute to the reported association between δENaC and blood pressure."

Persistent Hypokalemia: A Manifestation of Long COVID Syndrome? (KIDNEY WEEK 2025) - "Initial oral potassium/Amiloride therapy improved potassium but caused intolerance, leading to weekly intravenous potassium chloride infusions, maintaining serum potassium around 3 mmol/L...Clinicians should consider Long COVID in new-onset persistent hypokalemia. Further research into prevalence and mechanisms is warranted."

Infectious Disease • Metabolic Disorders • Nephrology • Novel Coronavirus Disease • Renal Disease • Respiratory Diseases

Empagliflozin Counters Metolazone-Induced Hypomagnesemia and Modifies Renal Ion Transporters and Channels (KIDNEY WEEK 2025) - "Hydrochlorothiazide response test showed EMPA did not reverse MET-induced NCC inhibition, while furosemide response test showed NKCC2 activity did not differ among the treatment groups. However, amiloride response test suggests EMPA may further inhibit ENaC-dependent K + secretion. Abundance of pAQP2 was significantly lower in MET and higher in EMPA mice. Conclusion EMPA could correct drug-induced hypomagnesemia, though it exerts complex effects on renal ion channels and transporters in response to polyuria."

Metabolic Disorders • CALB1

Afferent Renal Nerve Activity Drives Chlorthalidone-Induced Salt Intake (KIDNEY WEEK 2025) - "Funding Other NIH Support Background High salt intake is a global public health concern and is linked to the development of hypertension, kidney disease, and millions of preventable deaths annually. CTD induced increases in ARNA were reduced by co-treatment with amiloride to 27.8%. Conclusion These studies support the hypothesis that ARDN decreases salt intake through an ENaC dependent mechanism, potentially leading to a novel treatment for high salt intake."

Anesthesia • Cardiovascular • Hypertension • Nephrology • Renal Disease

Piezo1 Mediates Deoxycorticosterone Acetate-Salt Hypertension Through Renal Epithelial Sodium Channel Activation in the Kidneys (KIDNEY WEEK 2025) - "Yoda1 markedly induced increased Na + influx in mpkCCD cells, which was significantly blocked by amiloride. ICG001 significantly attenuated the mechanical force or Yoda1-induced upregulation of β-catenin and ENaC subunits. Conclusion Piezo1 activation induced increased blood pressure likely through upregulating ENaC expression in the kidney of mice with DOCA-salt by activating β-catenin pathway."

Cardiovascular • Hypertension • Nephrology • Renal Disease

Utility of Acetazolamide in Lithium-Induced Arginine Vasopressin Resistance (KIDNEY WEEK 2025) - "Thiazides were avoided due to severe hypomagnesemia (0.9 mg/dL), attributed to diarrhea and panitumumab, and concern for Li toxicity. Desmopressin and amiloride failed to improve polyuria, and the patient required intravenous (IV) dextrose water to maintain normonatremia for a week due to poor oral intake...Although current evidence is largely from animal and congenital models, this case demonstrates successful use in an adult, allowing rapid IV fluid weaning and potentially shortening hospitalization. Acetazolamide may also offer a reduced risk of Li toxicity as it inhibits renal tubular reabsorption of Li, and fewer electrolyte disturbances compared to thiazide-based therapy, suggesting its potential for broader use in difficult-to-manage Li-induced AVR."

Anal Carcinoma • Bipolar Disorder • CNS Disorders • Infectious Disease • Mood Disorders • Nephrology • Psychiatry • Pulmonary Disease • Renal Disease • Squamous Cell Carcinoma

Roles Prostaglandins and Renin in ABCA1-Deficient Model of Hypertension (HTN) (KIDNEY WEEK 2025) - "Ussing studies showed that BL PGE2 induces an increase in short circuit current ( Isc ) to raise amiloride sensitive current ( Ia ) and this effect was more pronounced in PSC833 exposed cells. The PGE2-induced Ia was greater in PSC833 treated (19.3±1.5 μA/cm 2 ) than untreated cells (16.4±1.9 μA/cm 2 ; paired t-test, p<0.05). Conclusion Thus, ABCA1 ablation or antagonism induces pERK, COX2, renin and PGE2 secretion to enhance Ia in the renal collecting duct which we speculate contributes to the BP phenotype."

Cardiovascular • Hypertension • ABCA1 • MT-CO2

Blood Pressure Modulation Through Epithelial Sodium Channel (ENaC) Alteration Induced by Microbiome Exchange Between Milan Normotensive and Hypertensive Rat Strains (KIDNEY WEEK 2025) - "Finally, MN-HOM showed a reduction in SBP comparable to MN-BSL after amiloride treatment with significantly enhanced urinary sodium excretion. Conclusion We have demonstrated that hypertensive phenotype in NA rats was transferred to MN rats through homogenization, indicating that gut microbiota or metabolites derived therefrom could modulate ENaC in the cortex and eventually modulate SBP. Further studies are ongoing to identify metabolites from gut microbiota which may modulate ENaC and eventually blood pressure."

Preclinical • Cardiovascular • Diabetes • Genetic Disorders • Hypertension • Metabolic Disorders • Obesity