Pub Date : 2026-03-01Epub Date: 2026-01-05DOI: 10.1016/j.xkme.2026.101246
Victoria J. Riehl-Tonn , David D.M. Nicholl , Paul E. Ronksley , Jennifer M. MacRae , Sandra M. Dumanski , Meghan J. Elliott , Colleen M. Norris , David Collister , Heather Ganshorn , Sofia B. Ahmed
<div><h3>Rationale & Objective</h3><div>The female survival advantage is diminished with hemodialysis. We evaluated the associations between measures of hemodialysis adequacy and quality and cardiovascular outcomes and mortality by sex.</div></div><div><h3>Study Design</h3><div>Systematic review of randomized controlled trials and observational studies. Electronic databases (MEDLINE, EMBASE, CENTRAL) were searched from inception to August 1, 2024.</div></div><div><h3>Setting & Study Populations</h3><div>Adults living with kidney failure treated with maintenance hemodialysis, stratified by sex.</div></div><div><h3>Selection Criteria for Studies</h3><div>Studies comparing higher versus lower measures of hemodialysis adequacy and quality (Kt/V, urea reduction ratio, ultrafiltration rate, treatment time) as exposures and reporting mortality (cardiovascular-related, all-cause), major adverse cardiovascular events, or cardiovascular-related hospitalization as outcomes.</div></div><div><h3>Data Extraction</h3><div>Data were extracted independently in duplicate.</div></div><div><h3>Analytical Approach</h3><div>Results were synthesized following Synthesis Without Meta-analysis reporting guidelines.</div></div><div><h3>Results</h3><div>Thirty-one studies (n = 1,402,002 participants) reported results by sex; only 10 studies reported the interaction by sex. Multiple measures of adequacy with varying definitions of ‘higher’ and ‘lower’ values were reported, with Kt/V being the most common. Three studies reported a greater decrease in all-cause mortality in female than in male individuals with higher single-pool Kt/V; 1 study reported no difference by sex. One study reported a greater decrease in all-cause mortality in female than in male individuals with higher urea reduction ratio; 1 study reported no difference by sex. One study reported a greater decrease in all-cause mortality in female than in male individuals with greater weekly hemodialysis treatment times; 1 study reported no difference by sex. Two studies reported greater all-cause mortality with higher ultrafiltration rate in female than in male individuals.</div></div><div><h3>Limitations</h3><div>Inconsistent reporting of hemodialysis adequacy and quality measures. Inconsistent inclusion of factors known to impact important clinical outcomes.</div></div><div><h3>Conclusions</h3><div>Although the results should be interpreted with caution due to significant study heterogeneity, female individuals may derive greater benefit from higher values of hemodialysis adequacy and quality measures than male individuals.</div></div><div><h3>Plain-Language Summary</h3><div>Female individuals treated with maintenance hemodialysis have lower survival compared to male individuals, which may be linked to current hemodialysis adequacy and quality targets that do not account for potential sex-based differences. Our study systematically reviewed the literature to compare the associations between measures of he
{"title":"Sex Differences in Associations Between Measures of Hemodialysis Adequacy and Quality, Cardiovascular Outcomes, and Mortality: A Systematic Review","authors":"Victoria J. Riehl-Tonn , David D.M. Nicholl , Paul E. Ronksley , Jennifer M. MacRae , Sandra M. Dumanski , Meghan J. Elliott , Colleen M. Norris , David Collister , Heather Ganshorn , Sofia B. Ahmed","doi":"10.1016/j.xkme.2026.101246","DOIUrl":"10.1016/j.xkme.2026.101246","url":null,"abstract":"<div><h3>Rationale & Objective</h3><div>The female survival advantage is diminished with hemodialysis. We evaluated the associations between measures of hemodialysis adequacy and quality and cardiovascular outcomes and mortality by sex.</div></div><div><h3>Study Design</h3><div>Systematic review of randomized controlled trials and observational studies. Electronic databases (MEDLINE, EMBASE, CENTRAL) were searched from inception to August 1, 2024.</div></div><div><h3>Setting & Study Populations</h3><div>Adults living with kidney failure treated with maintenance hemodialysis, stratified by sex.</div></div><div><h3>Selection Criteria for Studies</h3><div>Studies comparing higher versus lower measures of hemodialysis adequacy and quality (Kt/V, urea reduction ratio, ultrafiltration rate, treatment time) as exposures and reporting mortality (cardiovascular-related, all-cause), major adverse cardiovascular events, or cardiovascular-related hospitalization as outcomes.</div></div><div><h3>Data Extraction</h3><div>Data were extracted independently in duplicate.</div></div><div><h3>Analytical Approach</h3><div>Results were synthesized following Synthesis Without Meta-analysis reporting guidelines.</div></div><div><h3>Results</h3><div>Thirty-one studies (n = 1,402,002 participants) reported results by sex; only 10 studies reported the interaction by sex. Multiple measures of adequacy with varying definitions of ‘higher’ and ‘lower’ values were reported, with Kt/V being the most common. Three studies reported a greater decrease in all-cause mortality in female than in male individuals with higher single-pool Kt/V; 1 study reported no difference by sex. One study reported a greater decrease in all-cause mortality in female than in male individuals with higher urea reduction ratio; 1 study reported no difference by sex. One study reported a greater decrease in all-cause mortality in female than in male individuals with greater weekly hemodialysis treatment times; 1 study reported no difference by sex. Two studies reported greater all-cause mortality with higher ultrafiltration rate in female than in male individuals.</div></div><div><h3>Limitations</h3><div>Inconsistent reporting of hemodialysis adequacy and quality measures. Inconsistent inclusion of factors known to impact important clinical outcomes.</div></div><div><h3>Conclusions</h3><div>Although the results should be interpreted with caution due to significant study heterogeneity, female individuals may derive greater benefit from higher values of hemodialysis adequacy and quality measures than male individuals.</div></div><div><h3>Plain-Language Summary</h3><div>Female individuals treated with maintenance hemodialysis have lower survival compared to male individuals, which may be linked to current hemodialysis adequacy and quality targets that do not account for potential sex-based differences. Our study systematically reviewed the literature to compare the associations between measures of he","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 3","pages":"Article 101246"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146181110","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}
Pub Date : 2026-03-01Epub Date: 2026-01-08DOI: 10.1016/j.xkme.2026.101248
Yu-Cheng Chiang , Dao-Fu Dai , Yi-Wen Chiu , Hugo Y.-H. Lin
<div><h3>Rationale & Objective</h3><div>Sodium-glucose cotransporter-2 inhibitors (SGLT2is) provide cardiovascular and renal benefits in individuals with or without type 2 diabetes. This systematic review and meta-analysis investigated the risks of acute kidney injury and other adverse events (AEs) associated with SGLT2is across diverse populations.</div></div><div><h3>Study Design</h3><div>Systematic review and meta-analysis of randomized controlled trials (RCTs).</div></div><div><h3>Setting & Study Populations</h3><div>Thirteen RCTs comprising 84,581 participants were included. The studies encompassed diverse populations, varying in diabetes status, presence of chronic kidney disease, and SGLT2i dosages.</div></div><div><h3>Selection Criteria for Studies</h3><div>We included RCTs published through December 31, 2023, that evaluated the safety and efficacy of SGLT2is and reported renal and nonrenal adverse outcomes.</div></div><div><h3>Data Extraction</h3><div>Two reviewers independently extracted data and resolved discrepancies by consensus, focusing on renal and nonrenal AEs and subgroup analyses.</div></div><div><h3>Analytical Approach</h3><div>Random-effects meta-analysis was performed to estimate pooled relative risks or odds ratios with 95% confidence intervals (CIs). Heterogeneity was assessed using the I<sup>2</sup> statistic.</div></div><div><h3>Results</h3><div>SGLT2is were associated with a 20% reduction in the risk of acute kidney injury (relative risk, 0.80; 95% CI, 0.74-0.87), with low between-study heterogeneity, supporting a consistent renoprotective effect. Among patients with chronic kidney disease, the risk of renal composite outcomes was also significantly reduced (odds ratio, 0.70; 95% CI, 0.62-0.79). However, treatment was associated with increased risks of genital infections (<em>P</em> < 0.001), urinary tract infections (<em>P</em> = 0.03), diabetic ketoacidosis (<em>P</em> < 0.001), and hypovolemia (<em>P</em> = 0.008). No significant differences were observed for hypoglycemia (<em>P</em> = 0.08) or lower limb amputation (<em>P</em> = 0.07).</div></div><div><h3>Limitations</h3><div>Variability in study design, definitions of AEs, and patient baseline characteristics may influence the findings.</div></div><div><h3>Conclusions</h3><div>SGLT2is conferred substantial renoprotective benefits but increases the risk of certain nonrenal AEs. Tailored treatment and close monitoring are crucial to ensure safety and efficacy, especially in high-risk patients.</div></div><div><h3>Plain-language Summary</h3><div>Doctors are exploring new ways to protect the kidneys, especially in people at risk for acute kidney injury (AKI), a sudden loss of kidney function. Medications called sodium-glucose cotransporter-2 inhibitors (SGLT2is), first used to treat diabetes, have shown promise for kidney and heart protection. We reviewed data from major clinical trials to see if these drugs help lower the risk of AKI. Our findings showed
{"title":"Sodium-Glucose Cotransporter-2 Inhibitors and Acute Kidney Injury Risk: A Systematic Review and Meta-Analysis of Randomized Trials","authors":"Yu-Cheng Chiang , Dao-Fu Dai , Yi-Wen Chiu , Hugo Y.-H. Lin","doi":"10.1016/j.xkme.2026.101248","DOIUrl":"10.1016/j.xkme.2026.101248","url":null,"abstract":"<div><h3>Rationale & Objective</h3><div>Sodium-glucose cotransporter-2 inhibitors (SGLT2is) provide cardiovascular and renal benefits in individuals with or without type 2 diabetes. This systematic review and meta-analysis investigated the risks of acute kidney injury and other adverse events (AEs) associated with SGLT2is across diverse populations.</div></div><div><h3>Study Design</h3><div>Systematic review and meta-analysis of randomized controlled trials (RCTs).</div></div><div><h3>Setting & Study Populations</h3><div>Thirteen RCTs comprising 84,581 participants were included. The studies encompassed diverse populations, varying in diabetes status, presence of chronic kidney disease, and SGLT2i dosages.</div></div><div><h3>Selection Criteria for Studies</h3><div>We included RCTs published through December 31, 2023, that evaluated the safety and efficacy of SGLT2is and reported renal and nonrenal adverse outcomes.</div></div><div><h3>Data Extraction</h3><div>Two reviewers independently extracted data and resolved discrepancies by consensus, focusing on renal and nonrenal AEs and subgroup analyses.</div></div><div><h3>Analytical Approach</h3><div>Random-effects meta-analysis was performed to estimate pooled relative risks or odds ratios with 95% confidence intervals (CIs). Heterogeneity was assessed using the I<sup>2</sup> statistic.</div></div><div><h3>Results</h3><div>SGLT2is were associated with a 20% reduction in the risk of acute kidney injury (relative risk, 0.80; 95% CI, 0.74-0.87), with low between-study heterogeneity, supporting a consistent renoprotective effect. Among patients with chronic kidney disease, the risk of renal composite outcomes was also significantly reduced (odds ratio, 0.70; 95% CI, 0.62-0.79). However, treatment was associated with increased risks of genital infections (<em>P</em> < 0.001), urinary tract infections (<em>P</em> = 0.03), diabetic ketoacidosis (<em>P</em> < 0.001), and hypovolemia (<em>P</em> = 0.008). No significant differences were observed for hypoglycemia (<em>P</em> = 0.08) or lower limb amputation (<em>P</em> = 0.07).</div></div><div><h3>Limitations</h3><div>Variability in study design, definitions of AEs, and patient baseline characteristics may influence the findings.</div></div><div><h3>Conclusions</h3><div>SGLT2is conferred substantial renoprotective benefits but increases the risk of certain nonrenal AEs. Tailored treatment and close monitoring are crucial to ensure safety and efficacy, especially in high-risk patients.</div></div><div><h3>Plain-language Summary</h3><div>Doctors are exploring new ways to protect the kidneys, especially in people at risk for acute kidney injury (AKI), a sudden loss of kidney function. Medications called sodium-glucose cotransporter-2 inhibitors (SGLT2is), first used to treat diabetes, have shown promise for kidney and heart protection. We reviewed data from major clinical trials to see if these drugs help lower the risk of AKI. Our findings showed","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 3","pages":"Article 101248"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147326476","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}
Pub Date : 2026-03-01Epub Date: 2026-01-30DOI: 10.1016/j.xkme.2026.101281
Vladimir Mushailov, Jai Radhakrishnan
{"title":"Corrigendum to “New and Emerging Nonimmunosuppressive Drug Therapies for Primary Adult Glomerular Diseases”","authors":"Vladimir Mushailov, Jai Radhakrishnan","doi":"10.1016/j.xkme.2026.101281","DOIUrl":"10.1016/j.xkme.2026.101281","url":null,"abstract":"","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 3","pages":"Article 101281"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147326627","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}
Pub Date : 2026-03-01Epub Date: 2026-01-10DOI: 10.1016/j.xkme.2026.101260
Lixing Xu , Jack Kit-Chung Ng , Gordon Chun-Kau Chan , Winston Wing-Shing Fung , Kai-Ming Chow , Cheuk-Chun Szeto
<div><h3>Rationale & Objective</h3><div>Bioimpedance spectroscopy is a convenient method to measure lean tissue mass (LTM), which is commonly taken as the skeletal muscle mass, in peritoneal dialysis (PD) patients. We investigated the prognostic significance of LTM as the percentage of body weight (%LTM) and as the marker of sarcopenia in incident PD patients.</div></div><div><h3>Study Design</h3><div>A retrospective review of a prospective cohort.</div></div><div><h3>Setting & Participants</h3><div>349 incident PD patients in a single center.</div></div><div><h3>Predictor</h3><div>Baseline %LTM.</div></div><div><h3>Outcomes</h3><div>Patient survival, technique survival, peritonitis-free survival, peritonitis rate, hospitalization rate, and the duration of hospitalization.</div></div><div><h3>Analytical Approach</h3><div>Time-to-event survival analyses; linear regression for hospitalization.</div></div><div><h3>Results</h3><div>The 5-year patient survival rates were 50.2%, 55.3%, 61.0%, and 72.6% for patients with %LTM quartiles I-IV, respectively (log-rank test; <em>P</em> = 0.02). Multivariable Cox regression analysis confirmed that baseline %LTM was associated with patient survival (adjusted HR, 0.982; 95% CI, 0.966-0.999; <em>P</em> = 0.04). Baseline %LTM was also associated with peritonitis-free survival (adjusted HR, 0.983; 95% CI, 0.968-0.998; <em>P</em> = 0.031), but not technique survival. %LTM was also significantly and inversely associated with the hospitalization rate (<em>P</em> = 0.002) and the duration of hospitalization (<em>P</em> = 0.02). Yet, %LTM was unrelated to the 5-year technique survival (<em>P</em> = 0.29) and the peritonitis rate (<em>P</em> = 0.15). The number of hospital admissions was 2.72, 2.39, 2.36, and 1.67 per year of follow-up for quartiles I-IV of baseline %LTM (Jonckheere-Terpstra test; <em>P</em> = 0.002), and the duration of hospital stay was 23.31, 20.84, 22.27, and 13.96 d/y, respectively (<em>P</em> = 0.02).</div></div><div><h3>Limitations</h3><div>Observational study with baseline measures only.</div></div><div><h3>Conclusions</h3><div>Baseline %LTM as measured using bioimpedance spectroscopy is associated with patient survival, peritonitis-free survival, the number of hospital admissions, and the duration of hospital stay in incident PD patients.</div></div><div><h3>Plain-Language Summary</h3><div>Muscle wasting is a common problem in dialysis patients. In patients starting peritoneal dialysis, we measured their lean tissue mass using bioimpedance spectroscopy. We found that patients with higher percentages of lean tissue mass had better survival rates over 5 years, fewer and shorter hospital stays, and a lower risk of infection complications (peritonitis). Overall, measuring muscle mass in new peritoneal dialysis patients can help predict who is likely to do better with treatment and have fewer hospital problems, suggesting that monitoring and possibly improving muscle mass could be important
{"title":"Prognostic Significance of Baseline Lean Tissue Mass Percentage in Incident Peritoneal Dialysis Patients","authors":"Lixing Xu , Jack Kit-Chung Ng , Gordon Chun-Kau Chan , Winston Wing-Shing Fung , Kai-Ming Chow , Cheuk-Chun Szeto","doi":"10.1016/j.xkme.2026.101260","DOIUrl":"10.1016/j.xkme.2026.101260","url":null,"abstract":"<div><h3>Rationale & Objective</h3><div>Bioimpedance spectroscopy is a convenient method to measure lean tissue mass (LTM), which is commonly taken as the skeletal muscle mass, in peritoneal dialysis (PD) patients. We investigated the prognostic significance of LTM as the percentage of body weight (%LTM) and as the marker of sarcopenia in incident PD patients.</div></div><div><h3>Study Design</h3><div>A retrospective review of a prospective cohort.</div></div><div><h3>Setting & Participants</h3><div>349 incident PD patients in a single center.</div></div><div><h3>Predictor</h3><div>Baseline %LTM.</div></div><div><h3>Outcomes</h3><div>Patient survival, technique survival, peritonitis-free survival, peritonitis rate, hospitalization rate, and the duration of hospitalization.</div></div><div><h3>Analytical Approach</h3><div>Time-to-event survival analyses; linear regression for hospitalization.</div></div><div><h3>Results</h3><div>The 5-year patient survival rates were 50.2%, 55.3%, 61.0%, and 72.6% for patients with %LTM quartiles I-IV, respectively (log-rank test; <em>P</em> = 0.02). Multivariable Cox regression analysis confirmed that baseline %LTM was associated with patient survival (adjusted HR, 0.982; 95% CI, 0.966-0.999; <em>P</em> = 0.04). Baseline %LTM was also associated with peritonitis-free survival (adjusted HR, 0.983; 95% CI, 0.968-0.998; <em>P</em> = 0.031), but not technique survival. %LTM was also significantly and inversely associated with the hospitalization rate (<em>P</em> = 0.002) and the duration of hospitalization (<em>P</em> = 0.02). Yet, %LTM was unrelated to the 5-year technique survival (<em>P</em> = 0.29) and the peritonitis rate (<em>P</em> = 0.15). The number of hospital admissions was 2.72, 2.39, 2.36, and 1.67 per year of follow-up for quartiles I-IV of baseline %LTM (Jonckheere-Terpstra test; <em>P</em> = 0.002), and the duration of hospital stay was 23.31, 20.84, 22.27, and 13.96 d/y, respectively (<em>P</em> = 0.02).</div></div><div><h3>Limitations</h3><div>Observational study with baseline measures only.</div></div><div><h3>Conclusions</h3><div>Baseline %LTM as measured using bioimpedance spectroscopy is associated with patient survival, peritonitis-free survival, the number of hospital admissions, and the duration of hospital stay in incident PD patients.</div></div><div><h3>Plain-Language Summary</h3><div>Muscle wasting is a common problem in dialysis patients. In patients starting peritoneal dialysis, we measured their lean tissue mass using bioimpedance spectroscopy. We found that patients with higher percentages of lean tissue mass had better survival rates over 5 years, fewer and shorter hospital stays, and a lower risk of infection complications (peritonitis). Overall, measuring muscle mass in new peritoneal dialysis patients can help predict who is likely to do better with treatment and have fewer hospital problems, suggesting that monitoring and possibly improving muscle mass could be important ","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 3","pages":"Article 101260"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147325716","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}
Pub Date : 2026-03-01Epub Date: 2026-01-08DOI: 10.1016/j.xkme.2026.101252
Rebecca Ryan , Thomas Fairhead , Sophie Seager , Mona Jain , Rauri Clark
Anti-glomerular basement membrane (anti-GBM) disease is typically mediated by IgG autoantibodies and presents with pulmonary hemorrhage and rapidly progressive glomerulonephritis, classically referred to as Goodpasture disease. We describe a novel IgA-mediated variant in a 53-year-old man with Crohn colitis, who presented with oligo-anuric acute kidney injury and hemoptysis. Despite having negative serology for anti-GBM antibodies, kidney biopsy revealed necrotizing crescentic glomerulonephritis with linear IgA deposition along the glomerular basement membrane. We suspect that a Crohn colitis flare may have incited a novel IgA-driven anti-GBM process which, remarkably, resolved in the absence of conventional immunosuppressive therapy, sharply deviating from previously reported IgA-mediated disease requiring aggressive intervention. Such a case suggests a possible link between abnormal IgA glycosylation in inflammatory bowel disease and the development of a unique IgA-mediated anti-GBM process. Recognition of this entity may broaden the diagnostic approach to seronegative pulmonary-renal syndromes and also highlight the potential for nonimmunosuppressive management.
{"title":"An Exceptional Case of Crohn-Associated IgA-Mediated Goodpasture Disease","authors":"Rebecca Ryan , Thomas Fairhead , Sophie Seager , Mona Jain , Rauri Clark","doi":"10.1016/j.xkme.2026.101252","DOIUrl":"10.1016/j.xkme.2026.101252","url":null,"abstract":"<div><div>Anti-glomerular basement membrane (anti-GBM) disease is typically mediated by IgG autoantibodies and presents with pulmonary hemorrhage and rapidly progressive glomerulonephritis, classically referred to as Goodpasture disease. We describe a novel IgA-mediated variant in a 53-year-old man with Crohn colitis, who presented with oligo-anuric acute kidney injury and hemoptysis. Despite having negative serology for anti-GBM antibodies, kidney biopsy revealed necrotizing crescentic glomerulonephritis with linear IgA deposition along the glomerular basement membrane. We suspect that a Crohn colitis flare may have incited a novel IgA-driven anti-GBM process which, remarkably, resolved in the absence of conventional immunosuppressive therapy, sharply deviating from previously reported IgA-mediated disease requiring aggressive intervention. Such a case suggests a possible link between abnormal IgA glycosylation in inflammatory bowel disease and the development of a unique IgA-mediated anti-GBM process. Recognition of this entity may broaden the diagnostic approach to seronegative pulmonary-renal syndromes and also highlight the potential for nonimmunosuppressive management.</div></div>","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 3","pages":"Article 101252"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146190426","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}
Pub Date : 2026-03-01Epub Date: 2025-12-26DOI: 10.1016/j.xkme.2025.101235
Sarah K. Nelson-Taylor , Jonathan Troost , Courtney Giannini , Colin Bauer , Tarak Srivastava , Jarcy Zee , Markus Bitzer , Laura Barisoni , llse Daehn , Julie A. Dougherty , William E. Smoyer , Bryce A. Kerlin , Audrey Fetsko , Imtiazul Islam , Xin Wang , Christine Sethna , Richard J. Johnson , Carmen de Lucas Collantes , Kazunari Kaneko , Gabriel Cara-Fuentes
<div><h3>Rationale & Objective</h3><div>Idiopathic nephrotic syndrome (INS) is viewed as a podocyte-specific disease. Recent reports indicate endothelial involvement, but its significance is unclear. Here, we investigated the relationship between the glomerular expression of selected genes relevant to endothelial health and clinical markers of disease severity.</div></div><div><h3>Study Design</h3><div>A cross-sectional study.</div></div><div><h3>Setting & Participants</h3><div>Patients with INS (n = 70 minimal change disease and n = 83 focal segmental glomerulosclerosis) from the Nephrotic Syndrome Study Network cohort study and 53 control participants. Validation studies, including animal and cell culture experiments, were performed.</div></div><div><h3>Exposure</h3><div>Gene expression analysis from micro-dissected human glomeruli. The study is focused on 10 genes highly relevant for endothelial homeostasis and barrier integrity (nitric oxide synthase 3 [<em>NOS3</em>], endothelial cell adhesion molecule, and endothelial cell specific molecule 1 [<em>ESM1</em>]), endothelial glycocalyx remodeling (<em>HPSE, HYAL1, MMP2, MMP9</em>, and <em>ADAMTS1</em>), and endothelial activation (<em>ICAM1 and CAV1</em>).</div></div><div><h3>Outcomes</h3><div>Kidney function, ultrastructural changes in podocytes and glomerular endothelium, interstitial fibrosis and tubular atrophy.</div></div><div><h3>Analytical Approach</h3><div>One-way ANOVA and Tukey’s multiple comparisons test, Pearson Correlation and Cohen’s d statistics.</div></div><div><h3>Results</h3><div>Transcriptomic analysis revealed that all genes of interest were highly expressed in glomeruli from INS patients compared with controls, except for <em>ESM1</em> and <em>MMP9</em>, which were decreased. Expression of endothelial-specific genes correlated with those of glycocalyx injury and cell activation. <em>HPSE</em>, <em>ADAMTS1</em>, <em>ICAM1</em>, and <em>CAV1</em> expression was inversely associated with kidney function, whereas ADAMTS1 showed a positive association with proteinuria. <em>NOS3</em>, <em>HPSE</em>, and <em>ADAMTS1</em> were associated with podocyte foot process effacement, and <em>ICAM1</em> with podocyte detachment. <em>HPSE</em> and <em>MMP2</em> were associated with ultrastructural endothelial injury, whereas <em>HPSE</em>, <em>MMP2</em>, <em>ICAM1</em>, and <em>CAV1</em> were associated with interstitial fibrosis and tubular atrophy. Several genes (<em>ESM1</em>, <em>HPSE</em>, <em>HYAL1</em>, <em>MMP2</em>, and <em>ICAM1</em>) were also dysregulated in experimental INS and validated in cultured glomerular endothelial cells (<em>NOS3</em> and heparanase) following exposure to INS sera.</div></div><div><h3>Limitations</h3><div>Observational study, selection bias, unmeasured confounders.</div></div><div><h3>Conclusions</h3><div>INS involves dysregulation of genes relevant for endothelial health.</div></div><div><h3>Plain-Language Summary</h3><div>Idiopathic Nephrotic
{"title":"Glomerular Transcriptome Analysis Reveals Endothelial Disturbances in Patients With Idiopathic Nephrotic Syndrome","authors":"Sarah K. Nelson-Taylor , Jonathan Troost , Courtney Giannini , Colin Bauer , Tarak Srivastava , Jarcy Zee , Markus Bitzer , Laura Barisoni , llse Daehn , Julie A. Dougherty , William E. Smoyer , Bryce A. Kerlin , Audrey Fetsko , Imtiazul Islam , Xin Wang , Christine Sethna , Richard J. Johnson , Carmen de Lucas Collantes , Kazunari Kaneko , Gabriel Cara-Fuentes","doi":"10.1016/j.xkme.2025.101235","DOIUrl":"10.1016/j.xkme.2025.101235","url":null,"abstract":"<div><h3>Rationale & Objective</h3><div>Idiopathic nephrotic syndrome (INS) is viewed as a podocyte-specific disease. Recent reports indicate endothelial involvement, but its significance is unclear. Here, we investigated the relationship between the glomerular expression of selected genes relevant to endothelial health and clinical markers of disease severity.</div></div><div><h3>Study Design</h3><div>A cross-sectional study.</div></div><div><h3>Setting & Participants</h3><div>Patients with INS (n = 70 minimal change disease and n = 83 focal segmental glomerulosclerosis) from the Nephrotic Syndrome Study Network cohort study and 53 control participants. Validation studies, including animal and cell culture experiments, were performed.</div></div><div><h3>Exposure</h3><div>Gene expression analysis from micro-dissected human glomeruli. The study is focused on 10 genes highly relevant for endothelial homeostasis and barrier integrity (nitric oxide synthase 3 [<em>NOS3</em>], endothelial cell adhesion molecule, and endothelial cell specific molecule 1 [<em>ESM1</em>]), endothelial glycocalyx remodeling (<em>HPSE, HYAL1, MMP2, MMP9</em>, and <em>ADAMTS1</em>), and endothelial activation (<em>ICAM1 and CAV1</em>).</div></div><div><h3>Outcomes</h3><div>Kidney function, ultrastructural changes in podocytes and glomerular endothelium, interstitial fibrosis and tubular atrophy.</div></div><div><h3>Analytical Approach</h3><div>One-way ANOVA and Tukey’s multiple comparisons test, Pearson Correlation and Cohen’s d statistics.</div></div><div><h3>Results</h3><div>Transcriptomic analysis revealed that all genes of interest were highly expressed in glomeruli from INS patients compared with controls, except for <em>ESM1</em> and <em>MMP9</em>, which were decreased. Expression of endothelial-specific genes correlated with those of glycocalyx injury and cell activation. <em>HPSE</em>, <em>ADAMTS1</em>, <em>ICAM1</em>, and <em>CAV1</em> expression was inversely associated with kidney function, whereas ADAMTS1 showed a positive association with proteinuria. <em>NOS3</em>, <em>HPSE</em>, and <em>ADAMTS1</em> were associated with podocyte foot process effacement, and <em>ICAM1</em> with podocyte detachment. <em>HPSE</em> and <em>MMP2</em> were associated with ultrastructural endothelial injury, whereas <em>HPSE</em>, <em>MMP2</em>, <em>ICAM1</em>, and <em>CAV1</em> were associated with interstitial fibrosis and tubular atrophy. Several genes (<em>ESM1</em>, <em>HPSE</em>, <em>HYAL1</em>, <em>MMP2</em>, and <em>ICAM1</em>) were also dysregulated in experimental INS and validated in cultured glomerular endothelial cells (<em>NOS3</em> and heparanase) following exposure to INS sera.</div></div><div><h3>Limitations</h3><div>Observational study, selection bias, unmeasured confounders.</div></div><div><h3>Conclusions</h3><div>INS involves dysregulation of genes relevant for endothelial health.</div></div><div><h3>Plain-Language Summary</h3><div>Idiopathic Nephrotic ","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 3","pages":"Article 101235"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142844","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}
Three months after starting 25 mg chlorthalidone, a patient was admitted to the medical intensive care unit to manage hypokalemia, metabolic alkalosis, hypo-osmolar hyponatremia, hyperglycemia, and 30 lb weight loss. The patient received ∼936 mEq potassium over 8 days, of which 456 mEq was administered during the first 2 days of admission. In the first 24 hours, the individual received intravenous fluids that delivered 406 mEq sodium chloride. By day 2, serum potassium level increased from 2.5 to 3.0 mEq/L, bicarbonate fell from 40 to 35 mEq/L, serum sodium improved from 121 to 134 mEq/L, and serum glucose levels improved from the 400s to the 200s (mg/dL). On day 4, serum chemistries normalized. Twenty-four hours after admission, serum aldosterone level and renin activity were unremarkable, and brain natriuretic peptide concentration was <10 pg/mL. The primary therapeutic interventions were potassium chloride replacement, modest sodium chloride replacement, and subcutaneous insulin administration. Natera Renasight genetic testing identified a pathologic missense variant (p.Glu121Asp) in a single allele of the thiazide-sensitive Na+/Cl− cotransporter, solute carrier family 12 member 3 (SLC12A3). We speculate that chlorthalidone unmasked a Gitelman syndrome-like phenotype in a patient with a single functional SLC12A3 allele. Moreover, this case informs us of the interrelationships of total body potassium depletion and glucose metabolism and systemic blood pressure.
{"title":"Unmasking of a Heterozygous SLC12A3 Variant","authors":"Chang Xu , Pietra Greenberg , Moses Bachan , Rajeev Rohatgi","doi":"10.1016/j.xkme.2026.101255","DOIUrl":"10.1016/j.xkme.2026.101255","url":null,"abstract":"<div><div>Three months after starting 25 mg chlorthalidone, a patient was admitted to the medical intensive care unit to manage hypokalemia, metabolic alkalosis, hypo-osmolar hyponatremia, hyperglycemia, and 30 lb weight loss. The patient received ∼936 mEq potassium over 8 days, of which 456 mEq was administered during the first 2 days of admission. In the first 24 hours, the individual received intravenous fluids that delivered 406 mEq sodium chloride. By day 2, serum potassium level increased from 2.5 to 3.0 mEq/L, bicarbonate fell from 40 to 35 mEq/L, serum sodium improved from 121 to 134 mEq/L, and serum glucose levels improved from the 400s to the 200s (mg/dL). On day 4, serum chemistries normalized. Twenty-four hours after admission, serum aldosterone level and renin activity were unremarkable, and brain natriuretic peptide concentration was <10 pg/mL. The primary therapeutic interventions were potassium chloride replacement, modest sodium chloride replacement, and subcutaneous insulin administration. Natera Renasight genetic testing identified a pathologic missense variant (p.Glu121Asp) in a single allele of the thiazide-sensitive Na<sup>+</sup>/Cl<sup>−</sup> cotransporter, solute carrier family 12 member 3 (<em>SLC12A3</em>). We speculate that chlorthalidone unmasked a Gitelman syndrome-like phenotype in a patient with a single functional <em>SLC12A3</em> allele. Moreover, this case informs us of the interrelationships of total body potassium depletion and glucose metabolism and systemic blood pressure.</div></div>","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 3","pages":"Article 101255"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147326492","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}
Pub Date : 2026-03-01Epub Date: 2026-01-06DOI: 10.1016/j.xkme.2026.101242
Abdallah S. Geara , Kelly B. Chen , Whitney Simmons
The clinical presentation and disease course of immunoglobulin A nephropathy (IgAN), the most common primary glomerular disease worldwide, vary considerably from patient to patient, often prolonging and complicating the diagnostic process. Additionally, the IgAN treatment landscape is rapidly changing, with ongoing development of numerous new agents targeting the underlying disease mechanism for greater efficacy. The variability of IgAN disease presentation and progression, the often complex path to diagnosis, and the evolving treatment landscape may pose significant challenges for patients and health care providers along the clinical journey. Furthermore, many factors associated with the health care system, providers, and patients may affect IgAN diagnosis, treatment, and management. This report uses the clinical and personal experiences and perspectives of the authors—a nephrologist treating patients with IgAN, an ambulatory nephrology nurse practitioner diagnosed with IgAN, and an ambulatory infusion center nurse practitioner diagnosed with IgAN—to depict the patient journey with this condition from the first clinical presentation through to long-term management. The clinical journey may be improved by increasing provider awareness of IgAN and its patient impact, as well as encouraging self-advocacy among patients.
{"title":"Patient and Provider Perspectives on the Patient Journey in Immunoglobulin A Nephropathy","authors":"Abdallah S. Geara , Kelly B. Chen , Whitney Simmons","doi":"10.1016/j.xkme.2026.101242","DOIUrl":"10.1016/j.xkme.2026.101242","url":null,"abstract":"<div><div>The clinical presentation and disease course of immunoglobulin A nephropathy (IgAN), the most common primary glomerular disease worldwide, vary considerably from patient to patient, often prolonging and complicating the diagnostic process. Additionally, the IgAN treatment landscape is rapidly changing, with ongoing development of numerous new agents targeting the underlying disease mechanism for greater efficacy. The variability of IgAN disease presentation and progression, the often complex path to diagnosis, and the evolving treatment landscape may pose significant challenges for patients and health care providers along the clinical journey. Furthermore, many factors associated with the health care system, providers, and patients may affect IgAN diagnosis, treatment, and management. This report uses the clinical and personal experiences and perspectives of the authors—a nephrologist treating patients with IgAN, an ambulatory nephrology nurse practitioner diagnosed with IgAN, and an ambulatory infusion center nurse practitioner diagnosed with IgAN—to depict the patient journey with this condition from the first clinical presentation through to long-term management. The clinical journey may be improved by increasing provider awareness of IgAN and its patient impact, as well as encouraging self-advocacy among patients.</div></div>","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 3","pages":"Article 101242"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147326597","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}
Pub Date : 2026-03-01Epub Date: 2026-01-10DOI: 10.1016/j.xkme.2026.101259
Reed Jaworski BS , Afolarin Amodu MD, MPH , Jing Liu MD , Ashish Verma MBBS , Ragnar Palsson MD , Isaac E. Stillman MD , Bryan R. Kestenbaum , Sushrut S. Waikar MD, MPH , Anand Srivastava MD, MPH
{"title":"The Association of Urine Albumin to Protein Ratio With Kidney Disease Progression","authors":"Reed Jaworski BS , Afolarin Amodu MD, MPH , Jing Liu MD , Ashish Verma MBBS , Ragnar Palsson MD , Isaac E. Stillman MD , Bryan R. Kestenbaum , Sushrut S. Waikar MD, MPH , Anand Srivastava MD, MPH","doi":"10.1016/j.xkme.2026.101259","DOIUrl":"10.1016/j.xkme.2026.101259","url":null,"abstract":"","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 3","pages":"Article 101259"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147326571","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}
Pub Date : 2026-03-01Epub Date: 2026-01-12DOI: 10.1016/j.xkme.2026.101261
Jyotirmoy Sarker , Abdullah I. Abdelaziz , Jacob Crook , Richard E. Nelson , Joanne LaFleur , Heather Nyman , Chao-Chin Lu , Kibum Kim
<div><h3>Rationale & Objective</h3><div>Efficient risk stratification is essential to optimize care and allocate resources for treatment of diabetic kidney disease (DKD). This study evaluates the cost-effectiveness of an artificial intelligence-driven in vitro kidney disease risk assay (AIKD).</div></div><div><h3>Study Design</h3><div>Cost-effectiveness analysis using a hybrid model, combining a decision tree followed by a Markov model.</div></div><div><h3>Setting & Population</h3><div>Patients with early-stage DKD receiving care within the US Veterans Health Administration health care system.</div></div><div><h3>Intervention(s)</h3><div>Risk stratification using AIKD versus Kidney Disease: Improving Global Outcomes (KDIGO) standard of care (SoC).</div></div><div><h3>Outcomes</h3><div>Five-year health care costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER).</div></div><div><h3>Model, Perspective, & Timeframe</h3><div>The decision tree delineated clinical pathways based on the prevalence of progressive decline in kidney function and risk stratification performance of AIKD versus KDIGO. The subsequent Markov model simulated DKD stage transitions across the underlying risk–treatment pathways. Model inputs included test performance characteristics, risk prevalence, transition probabilities, costs, and utilities. One-way and probabilistic sensitivity analyses assessed uncertainty. The analysis was conducted from the perspective of the Veterans Health Administration health care system over a 5-year time horizon.</div></div><div><h3>Results</h3><div>AIKD-guided care resulted in a total cost of $146,437 and 2.8277 QALYs, compared with $145,120 and 2.8164 QALYs for the SoC arm. The ICER for AIKD relative to SoC was $116,349 per QALY gained. One-way sensitivity analysis showed that the sensitivity and specificity of AIKD and SoC, as well as the prevalence of underlying risk of progressive decline in kidney function, were the most influential inputs affecting the ICER. From the probabilistic sensitivity analysis, AIKD has 69% likelihood of being accepted at the conventional willingness-to-pay threshold of $150,000 per QALY gained.</div></div><div><h3>Limitations</h3><div>Model assumptions regarding risk stratification performance and long-term treatment effects may limit generalizability.</div></div><div><h3>Conclusions</h3><div>AIKD is cost-effective compared to KDIGO for patients with early-stage DKD. Its adoption could improve health outcomes and support efficient health care resource utilization management.</div></div><div><h3>Plain-Language Summary</h3><div>We studied whether a new artificial intelligence tool, artificial intelligence-driven in vitro kidney disease risk assay (AIKD), is a worthwhile investment for early identification of diabetic kidney disease compared with the current Kidney Disease: Improving Global Outcomes (KDIGO) guideline-recommended risk stratification method. This tool assis
{"title":"Cost-Effectiveness Analysis of Artificial Intelligence-Driven Risk Stratification in Patients With Diabetic Kidney Disease in the US Veterans Population","authors":"Jyotirmoy Sarker , Abdullah I. Abdelaziz , Jacob Crook , Richard E. Nelson , Joanne LaFleur , Heather Nyman , Chao-Chin Lu , Kibum Kim","doi":"10.1016/j.xkme.2026.101261","DOIUrl":"10.1016/j.xkme.2026.101261","url":null,"abstract":"<div><h3>Rationale & Objective</h3><div>Efficient risk stratification is essential to optimize care and allocate resources for treatment of diabetic kidney disease (DKD). This study evaluates the cost-effectiveness of an artificial intelligence-driven in vitro kidney disease risk assay (AIKD).</div></div><div><h3>Study Design</h3><div>Cost-effectiveness analysis using a hybrid model, combining a decision tree followed by a Markov model.</div></div><div><h3>Setting & Population</h3><div>Patients with early-stage DKD receiving care within the US Veterans Health Administration health care system.</div></div><div><h3>Intervention(s)</h3><div>Risk stratification using AIKD versus Kidney Disease: Improving Global Outcomes (KDIGO) standard of care (SoC).</div></div><div><h3>Outcomes</h3><div>Five-year health care costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER).</div></div><div><h3>Model, Perspective, & Timeframe</h3><div>The decision tree delineated clinical pathways based on the prevalence of progressive decline in kidney function and risk stratification performance of AIKD versus KDIGO. The subsequent Markov model simulated DKD stage transitions across the underlying risk–treatment pathways. Model inputs included test performance characteristics, risk prevalence, transition probabilities, costs, and utilities. One-way and probabilistic sensitivity analyses assessed uncertainty. The analysis was conducted from the perspective of the Veterans Health Administration health care system over a 5-year time horizon.</div></div><div><h3>Results</h3><div>AIKD-guided care resulted in a total cost of $146,437 and 2.8277 QALYs, compared with $145,120 and 2.8164 QALYs for the SoC arm. The ICER for AIKD relative to SoC was $116,349 per QALY gained. One-way sensitivity analysis showed that the sensitivity and specificity of AIKD and SoC, as well as the prevalence of underlying risk of progressive decline in kidney function, were the most influential inputs affecting the ICER. From the probabilistic sensitivity analysis, AIKD has 69% likelihood of being accepted at the conventional willingness-to-pay threshold of $150,000 per QALY gained.</div></div><div><h3>Limitations</h3><div>Model assumptions regarding risk stratification performance and long-term treatment effects may limit generalizability.</div></div><div><h3>Conclusions</h3><div>AIKD is cost-effective compared to KDIGO for patients with early-stage DKD. Its adoption could improve health outcomes and support efficient health care resource utilization management.</div></div><div><h3>Plain-Language Summary</h3><div>We studied whether a new artificial intelligence tool, artificial intelligence-driven in vitro kidney disease risk assay (AIKD), is a worthwhile investment for early identification of diabetic kidney disease compared with the current Kidney Disease: Improving Global Outcomes (KDIGO) guideline-recommended risk stratification method. This tool assis","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 3","pages":"Article 101261"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147399573","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}
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