Kidney Medicine最新文献

{"title":"Functional Analysis of a Novel Pathogenic Glycine Amidinotransferase Mutant in Hereditary Fanconi Syndrome","authors":"Shunsuke Takayanagi ,&nbsp;Keita P. Mori ,&nbsp;Youngna Kang ,&nbsp;Mitsugu Araki ,&nbsp;Shigeyuki Matsumoto ,&nbsp;Yukari Sagae ,&nbsp;Nana Sakakibara ,&nbsp;Tomoko Horinouchi ,&nbsp;Yoshiaki Higashi ,&nbsp;Tomomi Endo ,&nbsp;Eri Muso ,&nbsp;Kandai Nozu ,&nbsp;Yasushi Okuno ,&nbsp;Motoko Yanagita ,&nbsp;Takeshi Matsubara ,&nbsp;Tatsuo Tsukamoto","doi":"10.1016/j.xkme.2026.101267","DOIUrl":"10.1016/j.xkme.2026.101267","url":null,"abstract":"<div><div>The mutant glycine amidinotransferase (GATM) protein polymerizes into a characteristic crystal, resulting in mitochondrial dysfunction in proximal tubules and Fanconi syndrome with progressive kidney failure. We identified a novel hereditary Fanconi syndrome characterized by mutant GATM proteins in a Japanese family, the first in Asia. Kidney biopsies exhibited typical histological features, confirmed by immunofluorescent staining with anti-GATM and anti-ATP synthase β subunit (ATPB) antibodies and electron microscopy. Quantitative immunofluorescence analysis showed a significant correlation between ATPB and GATM–ATPB colocalization, suggesting mitochondrial pathogenicity of the mutant. Previously reported GATM mutations, clustered in the fourth of 5 β-sheets of the GATM protein, are assumed to have increased adhesive properties, changing the β-sheet from its original dimeric form to a unique polymerization. Targeted panel sequencing showed a novel mutation (Q268E) in the <em>GATM</em> gene (NM_001482.3: c.802C&gt;G), distinct from this sheet. Because conventional methods failed to detect the significance, we employed an advanced molecular dynamics approach—hypersound-perturbed molecular dynamics simulations. This analysis effectively demonstrated that the Q268E mutation enhanced conformational flexibility of region-spanning residues that are spatially positioned between the mutated site and the sheet, leading to the pathological polymerization of the mutant protein. This simulation offers valuable insights into the pathological mechanisms of abnormal protein conformation.</div></div>","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 3","pages":"Article 101267"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147355560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multifactorial Predictors of Renal Outcomes in Alport Syndrome: Integrating Genetic, Clinical, and Cystic Phenotypes","authors":"Zhuo-ran Song ,&nbsp;Yang Li ,&nbsp;Zhi-ying Liu ,&nbsp;Meng-shi Li ,&nbsp;Yu-qing Chen ,&nbsp;Ji-cheng Lv ,&nbsp;Xu-jie Zhou ,&nbsp;Hong Zhang","doi":"10.1016/j.xkme.2026.101264","DOIUrl":"10.1016/j.xkme.2026.101264","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Rationale &amp; Objective&lt;/h3&gt;&lt;div&gt;Alport syndrome is an inherited kidney disease with significant clinical heterogeneity. This study aims to explore risk factors affecting the prognosis and investigates the relationship between kidney cysts and clinical manifestations in patients with Alport syndrome.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Study Design&lt;/h3&gt;&lt;div&gt;A single-center retrospective cohort study.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Setting &amp; Participants&lt;/h3&gt;&lt;div&gt;A total of 179 patients diagnosed with Alport syndrome in Peking University First Hospital.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Predictors&lt;/h3&gt;&lt;div&gt;Clinical characteristics (renal manifestations and extrarenal features), genetic patterns, and the presence of kidney cysts.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Outcomes&lt;/h3&gt;&lt;div&gt;Kidney failure with replacement therapy or chronic kidney disease stage 3b.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Analytical Approach&lt;/h3&gt;&lt;div&gt;Kaplan-Meier survival analysis, Cox proportional hazards models, logistic regression models, and linear mixed models.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;In this Chinese adult Alport syndrome cohort, we identified several prognostic risk factors, including baseline serum creatinine (HR, 3.15; 95% CI, 1.95-5.08), proteinuria (HR, 1.29; 95% CI, 1.01-1.65), earlier diagnostic age (HR, 1.30; 95% CI, 1.16-1.45), male sex (HR, 3.00; 95% CI, 1.05-8.54), eye and ear impairment (HR, 19.49; 95% CI, 2.52-150.67), and inheritance mode (X-linked or autosomal recessive) (HR, 5.46; 95% CI, 1.47-20.30). Notably, 33.5% of patients with Alport syndrome presented with kidney cysts, compared with only 12.8% in the matched IgA nephropathy cohort (&lt;em&gt;P&lt;/em&gt; &lt; 0.001). The presence of kidney cysts was associated with older age and faster estimated glomerular filtration rate (eGFR) decline, independent of inheritance patterns. In patients aged less than 40 years, those with kidney cysts exhibited significantly worse renal function (median eGFR, 72 vs 108 mL/min/1.73 m&lt;sup&gt;2&lt;/sup&gt;; &lt;em&gt;P&lt;/em&gt; = 0.002) and a nearly 2-fold faster decline in eGFR slope.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Limitations&lt;/h3&gt;&lt;div&gt;Selection bias, absence of time-varying cyst observations, and limitations in generalizability.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;Our study reveals that kidney cysts are associated with severe clinical manifestations in Alport syndrome, particularly in younger patients. This finding highlights the importance of monitoring kidney cysts in patients with Alport syndrome and suggests their potential role as a prognostic indicator.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Plain-Language Summary&lt;/h3&gt;&lt;div&gt;Alport syndrome, an inherited kidney disease, varies widely in severity, but the risk factors affecting outcomes and the role of kidney cysts remain unclear. We analyzed the medical records of 179 patients with Alport syndrome and found that more urinary protein, younger age at diagnosis, male sex, eye/ear impairment, and specific genetic patterns increased risks. Kidney cysts were common in patients with Alport syndrome and were linked to fa","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 3","pages":"Article 101264"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147326672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Unusual Case of 5-Oxoproline Acidosis","authors":"Nils Müller,&nbsp;Anne Krüger,&nbsp;Alexander Reshetnik","doi":"10.1016/j.xkme.2025.101236","DOIUrl":"10.1016/j.xkme.2025.101236","url":null,"abstract":"<div><div>Although metabolic acidosis is a common phenomenon, its differential diagnoses include a variety of rare conditions. Among the causes of high anion gap metabolic acidosis is an accumulation of 5-oxoproline or pyroglutamic acid. It is commonly understood that development can occur in the context of high-dose paracetamol intake and either relevant clinical risk factors or comedication with flucloxacillin or oxacillin. As a rare condition, it has become well-known only to specialized clinicians. We reported a case of high anion gap metabolic acidosis caused by 5-oxoproline in a middle-aged male treated only with high-dose flucloxacillin. Our patient had neither a history of paracetamol use nor classical risk factors to a degree, making the development of 5-oxoproline/pyroglutamic acidosis plausible. Although there have been plenty of case reports of this condition because of the coadministration of paracetamol/acetaminophen and flucloxacillin/oxacillin, to our knowledge, this is only the second published case of 5-oxoproline acidosis without paracetamol use, making it either highly unusual or potentially underdiagnosed. Therefore, we suggest considering 5-oxoproline/pyroglutamic acidosis when evaluating the etiology of metabolic acidosis in patients on high-dose flucloxacillin/oxacillin, even without a history of concomitant or previous paracetamol exposure or other classical risk factors.</div></div>","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 3","pages":"Article 101236"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146081364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Composite Primary Outcomes in Nephrology Clinical Trials","authors":"Steven Fishbane MD,&nbsp;Pratap Upadrista MBBS,&nbsp;Hitesh H. Shah MD","doi":"10.1016/j.xkme.2025.101231","DOIUrl":"10.1016/j.xkme.2025.101231","url":null,"abstract":"<div><div>Composite study endpoints have made it possible to reduce the sample size and lower the cost of certain clinical trials. In nephrology trials, the use of composite endpoints has led to opportunities but has also created challenges in the interpretation of study results. In this perspective, we review how composite outcomes work and why there are risks attendant to their use. We also provide examples of the use of composite outcomes from specific nephrology trials and certain problems that resulted.</div></div>","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 3","pages":"Article 101231"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146081367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How Far Is a Kidney Willing to Go? Kidney Transplant Outcomes Based on Distance Donor Kidney Travels to Transplant Centers","authors":"Nakul Datta ,&nbsp;Ahad Qureshi ,&nbsp;Mahsa Ebadyrad ,&nbsp;Phuong-Thu Thi Pham ,&nbsp;Anum Hamiduzzaman ,&nbsp;Afshin Pirzadeh ,&nbsp;Alexis Velazquez ,&nbsp;Suphamai Bunnapradist ,&nbsp;Erik L. Lum","doi":"10.1016/j.xkme.2026.101262","DOIUrl":"10.1016/j.xkme.2026.101262","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Rationale &amp; Objectives&lt;/h3&gt;&lt;div&gt;There are growing concerns over inequities and inequality in deceased-donor kidney access. The current allocation system emphasizes distance from the kidney donor, resulting in geographic disparities in kidney transplantation. Increasing the priority radius for deceased-donor kidneys may improve access; however, increasing the distance a kidney travels increases cold ischemia time and may result in worse allograft outcomes. We examined whether donor kidney travel distance is associated with posttransplant outcomes.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Study Design&lt;/h3&gt;&lt;div&gt;Retrospective cohort study.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Setting &amp; Participants&lt;/h3&gt;&lt;div&gt;A total of 210,698 deceased-donor kidney transplants performed in the United States from 2000-2020 that were identified in the Organ Procurement and Transplantation Network/United Network for Organ Sharing database.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Exposure&lt;/h3&gt;&lt;div&gt;Distances were grouped ≤ 50, 50-200, 200-500, 500-1,000, 1,000-2,000, and &gt;2,000 nautical miles from the transplant center.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Outcomes&lt;/h3&gt;&lt;div&gt;The primary outcome was death-censored graft survival. Secondary outcome measures were delayed graft function, primary nonfunction, and posttransplant serum creatinine levels.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Analytical Approach&lt;/h3&gt;&lt;div&gt;The Cox regression model with the Breslow method for ties was used to analyze survival data.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;A total of 210,698 deceased-donor kidney transplants were used in our analysis, and 15,147 kidney transplant recipients were eligible for the multivariable proportional hazard model. In total, 3,488 kidney transplant recipients experienced graft failure at 10 years. Geographic distance demonstrated no significant association with death-censored graft survival (hazard ratios [HRs] of 1.05, 1.11, 1.14, 1.03, and 0.80). Higher kidney donor profile index scores, recipient age, and presence of diabetes were associated with increased graft failure (HR, 1.52, 1.01, and 1.46, respectively). Preemptive transplant was associated with a reduced risk of graft failure (HR, 0.83).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Limitations&lt;/h3&gt;&lt;div&gt;Our study lacked organ discard rates and a limited number of high-kidney donor profile index scores and donations after cardiac death at longer distances.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;Donor kidney travel distance was not associated with reduced long-term graft survival. Expanding allocation radius or implementing a national sharing system may improve equity in access without compromising outcomes.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Plain-Language Summary&lt;/h3&gt;&lt;div&gt;Where a patient lives determines how long they have to wait for a deceased-donor kidney transplant. Currently, deceased-donor kidneys are prioritized for patients listed within 250 nautical miles of the deceased donor’s location. Our research examined whether the distance a kidney is transported results in worse organ survival. Our analysis of 2 deca","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 3","pages":"Article 101262"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147399571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to Letter by Ito and Mori","authors":"Hongwei Zhao MD","doi":"10.1016/j.xkme.2026.101307","DOIUrl":"10.1016/j.xkme.2026.101307","url":null,"abstract":"","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 3","pages":"Article 101307"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147399971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"When Hepatitis B Virus-Associated Glomerulonephritis Mimics Lupus Nephritis: A Case of Adult-Onset Disease With Full-House Pattern","authors":"Kei Kono ,&nbsp;Naoki Sawa ,&nbsp;Hiroki Mizuno ,&nbsp;Yuki Oba ,&nbsp;Noriko Inoue ,&nbsp;Akinari Sekine ,&nbsp;Kiho Tanaka ,&nbsp;Masayuki Yamanouchi ,&nbsp;Eiko Hasegawa ,&nbsp;Tatsuya Suwabe ,&nbsp;Satoshi Saitoh ,&nbsp;Takeshi Fujii ,&nbsp;Yutaka Takazawa ,&nbsp;Kenichi Ohashi ,&nbsp;Takehiko Wada ,&nbsp;Yoshifumi Ubara","doi":"10.1016/j.xkme.2026.101256","DOIUrl":"10.1016/j.xkme.2026.101256","url":null,"abstract":"<div><div>Although membranous nephritis represents the classic presentation of hepatitis B virus--associated glomerulonephritis (HBV-GN) in children, adult cases can exhibit quite different features. In 1992, a 41-year-old man with recurrent nephrotic syndrome since 20 years was admitted for renal evaluation and underwent kidney biopsy. Light microscopy showed periodic acid methenamine silver staining with spike formation consistent with membranous nephropathy. However, electron microscopy demonstrated large electron-dense deposits distributed throughout subepithelial, subendothelial, and mesangial areas—an unusual pattern. Immunofluorescence showed a complete “full-house” pattern with positive staining for immunoglobulin (Ig)G (IgG2-IgG4), IgA, IgM, C3, C4, and C1q along the glomerular basement membrane. These findings initially suggested lupus nephritis, but comprehensive autoimmune testing proved negative, including antinuclear antibodies and anti--double-stranded DNA antibodies, with no characteristic clinical manifestations. Further evaluation showed positive serum HBV e antigen and DNA polymerase. Crucially, tissue immunostaining confirmed HBV e antigen deposition along the glomerular basement membrane, with high-magnification electron microscopy revealing virus-like particles, establishing the diagnosis of HBV-GN. Unlike the typical membranous pattern seen in pediatric HBV-GN, this adult case demonstrated lupus-like features with diverse glomerular lesions. To our knowledge, this represents the first English-language publication of this diagnostically challenging case, highlighting the need for heightened awareness of atypical adult HBV-GN presentations.</div></div>","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 3","pages":"Article 101256"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147399972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complete Remission After Percutaneous Renal Artery Angioplasty for Focal Segmental Glomerulosclerosis due to Takayasu Disease: A Case Report","authors":"Yusuke Ushio ,&nbsp;Shun Manabe ,&nbsp;Anna Nakai ,&nbsp;Momoko Seki ,&nbsp;Shiho Makabe ,&nbsp;Shizuka Kobayashi ,&nbsp;Yuki Kawaguchi ,&nbsp;Hiroshi Kataoka ,&nbsp;Naoko Ito ,&nbsp;Sekiko Taneda ,&nbsp;Kazuho Honda ,&nbsp;Junichi Hoshino","doi":"10.1016/j.xkme.2026.101251","DOIUrl":"10.1016/j.xkme.2026.101251","url":null,"abstract":"<div><div>Renal artery stenosis is a common complication of Takayasu disease; however, the presence of nephrotic syndrome is rare. Percutaneous transluminal renal angioplasty (PTRA) is performed for renal artery stenosis; however, its efficacy is unclear for renal artery stenosis complicated with nephrotic syndrome. This is a case report of Takayasu disease in an 18-year-old woman with no relevant medical history. Magnetic resonance angiography revealed bilateral renal artery stenosis, and nephrotic syndrome was noted. Focal segmental glomerulosclerosis was diagnosed based on renal biopsy. As atrophy was observed in the right kidney, PTRA was performed for the left renal artery stenosis. Urine protein levels decreased subsequently, leading to remission. Renal artery stenosis may commonly occur due to Takayasu disease; however, the resulting accentuation of the renin-angiotensin-aldosterone cascade and increased intraglomerular pressure may cause focal segmental glomerulosclerosis. PTRA may induce remission if renal dysfunction is mild, and it should be performed as early as possible.</div></div>","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 3","pages":"Article 101251"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147326669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uptake of Newly Licensed Influenza Vaccine Formulations Among Patients Receiving Chronic Hemodialysis During the 2010/2011 to 2021/2022 Influenza Seasons","authors":"John M. Sahrmann MA ,&nbsp;J. Bradley Layton PhD ,&nbsp;Katelin B. Nickel MPH ,&nbsp;John W. Davis MD, PhD ,&nbsp;Vikas R. Dharnidharka MD, MPH ,&nbsp;David J. Weber MD, MPH ,&nbsp;Anne M. Butler PhD","doi":"10.1016/j.xkme.2026.101243","DOIUrl":"10.1016/j.xkme.2026.101243","url":null,"abstract":"","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 3","pages":"Article 101243"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of Low-Dose Tolvaptan for Treatment of Profound Hyponatremia in Syndrome of Inappropriate Antidiuresis (SIAD): The EFFLUX-FLUID TRIAL","authors":"Narongchai Jaiyen ,&nbsp;Sutatip Chinpraditsuk ,&nbsp;Pattharawin Pattharanitima ,&nbsp;Pichaya Tantiyavarong ,&nbsp;Pajaree Krisanapan","doi":"10.1016/j.xkme.2025.101239","DOIUrl":"10.1016/j.xkme.2025.101239","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Rationale &amp; Objective&lt;/h3&gt;&lt;div&gt;Although tolvaptan is effective for treating hyponatremia in the syndrome of inappropriate antidiuresis (SIAD), fluid restriction remains the first-line therapy because of safety concerns. This study evaluated whether low-dose tolvaptan is more effective than a combination of fluid restriction, furosemide, and sodium chloride tablets in patients with profound hyponatremia and clinical predictors of fluid restriction failure.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Study Design&lt;/h3&gt;&lt;div&gt;Single-center, open-label, randomized controlled trial.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Setting &amp; Participants&lt;/h3&gt;&lt;div&gt;Hospitalized adults with chronic SIAD and serum sodium concentration [Na&lt;sup&gt;+&lt;/sup&gt;] ≤125 mmol/L, meeting ≥ 1 predictor of fluid restriction failure (urine osmolality &gt;500 mOsm/kg H&lt;sub&gt;2&lt;/sub&gt;O, sum of urine sodium and potassium &gt; [Na&lt;sup&gt;+&lt;/sup&gt;], or urine volume &lt;1,500 mL/day). Twenty-nine patients were randomized (13 to tolvaptan, 16 to control).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Exposure(s)&lt;/h3&gt;&lt;div&gt;Tolvaptan 7.5 mg/day with liberal fluid intake versus fluid restriction (800 mL/day), furosemide (20-40 mg/day), and sodium chloride tablets (3 g/day) for 28 days.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Outcome(s)&lt;/h3&gt;&lt;div&gt;The primary outcome was change in [Na&lt;sup&gt;+&lt;/sup&gt;] from baseline to day 4. Secondary outcomes include change in [Na&lt;sup&gt;+&lt;/sup&gt;] through day 28, achievement of [Na&lt;sup&gt;+&lt;/sup&gt;] ≥130 mmol/L at day 4, time to correction, and adverse events.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Analytical Approach&lt;/h3&gt;&lt;div&gt;Intention-to-treat analysis using &lt;em&gt;t&lt;/em&gt; tests, Fisher exact test, Kaplan–Meier estimates, and generalized estimating equation models.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Mean baseline [Na&lt;sup&gt;+&lt;/sup&gt;] was 120 ± 3 mmol/L. By day 4, [Na&lt;sup&gt;+&lt;/sup&gt;] increased significantly more with tolvaptan (12.2 ± 3.4 vs 6.3 ± 6.0 mmol/L; &lt;em&gt;P&lt;/em&gt; = 0.004), with continued benefit on days 7 and 14. More patients achieved [Na&lt;sup&gt;+&lt;/sup&gt;] ≥130 mmol/L at day 4 (77% vs 25%; &lt;em&gt;P&lt;/em&gt; = 0.009), with shorter median time to correction (2 vs 14 days; &lt;em&gt;P&lt;/em&gt; = 0.02). Hypokalemia was less frequent with tolvaptan (8% vs 44%; &lt;em&gt;P&lt;/em&gt; = 0.04). Overcorrection occurred in 3 tolvaptan patients (23%) without clinical sequelae (&lt;em&gt;P&lt;/em&gt; = 0.08).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Limitations&lt;/h3&gt;&lt;div&gt;Small sample size and single-center design.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;Low-dose tolvaptan effectively and rapidly increases [Na&lt;sup&gt;+&lt;/sup&gt;] in SIAD patients with predictors of fluid restriction failure, with acceptable safety under close monitoring.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Plain-Language Summary&lt;/h3&gt;&lt;div&gt;Hyponatremia, or low blood sodium levels, is a common and potentially serious condition in hospitalized patients. Fluid restriction is the standard first-line treatment, but it is often ineffective in patients with the syndrome of inappropriate antidiuresis (SIAD). This study evaluated whether low-dose tolvaptan could improve outcomes in patients at high risk of fluid restrict","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 3","pages":"Article 101239"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}