Kidney360最新文献

{"title":"Socioeconomic Disparities in Preemptive Kidney Transplant Rates in Children.","authors":"Sarah Kizilbash, Chung-Ii Wi, Madison Roy, Warren T McKinney, Sandra Amaral, Samy Riad, Young Juhn","doi":"10.34067/KID.0000000802","DOIUrl":"https://doi.org/10.34067/KID.0000000802","url":null,"abstract":"<p><strong>Background: </strong>Preemptive kidney transplantation in children is associated with better patient and graft survival compared to transplants following dialysis. However, preemptive kidney transplantation rates in children remain low. This study aimed to evaluate the effect of socioeconomic status (SES) on preemptive transplantation in children.</p><p><strong>Methods: </strong>Our study included 173 Minnesota-resident pediatric kidney transplant recipients (<18 years) transplanted at the University of Minnesota from 2010-2020. Using the HOUSES index, a validated, individual SES measure based on housing units categorized into quartiles (Q1: lower SES; Q2-Q4: higher SES), we applied mixed-effects multivariable logistic models to examine the effects of HOUSES on preemptive kidney transplants and pretransplant dialysis duration.</p><p><strong>Results: </strong>Of 173 pediatric kidney transplant recipients, 46 (26.6%) received a preemptive transplant, and of 109 recipients with dialysis duration data, 39 (35.8%) received dialysis for >1 year. After adjusting for age at kidney failure, sex, donor type, insurance type, and underlying cause of kidney failure, we observed significantly lower odds of preemptive transplantation among Q1 recipients compared to Q2-4 recipients (Adjusted odds ratio [aOR]: 0.31; 95% CI: 0.11, 0.90; p=0.03).</p><p><strong>Conclusions: </strong>Using the HOUSES index, we found significant socioeconomic disparities in preemptive kidney transplantation rates among children.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795767","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":"Ameliorative Effect of an Anti-microRNA-21 Oligonucleotide on Animal and Human Models of Cystic Kidney Disease.","authors":"Yuhei Noda, Noritoshi Kato, Fuminori Sato, Yuji Suzuki, Shoma Tsubota, Hiroki Kitai, Shintaro Komatsu, Akihito Tanaka, Yuka Sato, Kayaho Maeda, Kazuhiro Furuhashi, Takuji Ishimoto, Tomoki Kosugi, Tamio Yamaguchi, Shizuko Nagao, Yukiko Kamiya, Kenji Kadomatsu, Hiroyuki Asanuma, Shoichi Maruyama","doi":"10.34067/KID.0000000771","DOIUrl":"https://doi.org/10.34067/KID.0000000771","url":null,"abstract":"<p><strong>Background: </strong>Hereditary cystic kidney diseases are ciliopathies characterized by functional defects in the primary cilia of renal tubules. Abnormalities in the primary cilia enhance cell proliferation signals and cause cyst enlargement. The most common type is autosomal dominant polycystic kidney disease (ADPKD), but other diseases, such as nephronophthisis, have been discovered to be more common than previously considered. In ADPKD, several microRNAs are reportedly aberrantly expressed and involved in disease pathogenesis. Among these, we focused on miR-21, which is upregulated in response to cAMP signaling. In this study, we aimed to newly generate an anti-miR-21 oligonucleotide synthesized from serinol nucleic acid (Anti-miR-21-SNA) to improve anti-miRNA activity and investigate its effects on cyst growth in vivo and in vitro.</p><p><strong>Methods: </strong>We evaluated the effectiveness of anti-miR-21 treatment using an SNA-based antisense oligonucleotide in a mouse model of cystic kidney disease and human ADPKD cells.</p><p><strong>Results: </strong>Our study revealed that Anti-miR-21-SNA effectively prevented cyst growth in vivo and in vitro. In the mouse model of cystic kidney disease, we systemically administered Anti-miR-21-SNA and observed its accumulation primarily in the kidneys, suggesting effective drug delivery. Anti-miR-21-SNA treatment reduced kidney size and blood urea nitrogen levels without inducing hepatotoxicity. Mechanistically, molecules related to mitochondrial metabolism, apoptosis, and fibrosis pathways were involved. In vitro, Anti-miR-21-SNA treatment of primary cultured kidney cells from an ADPKD patient reduced cyst volume and intracellular cAMP content and increased Ca2+ concentration, supporting the efficacy of this treatment.</p><p><strong>Conclusions: </strong>Our results showed that Anti-miR-21-SNA treatment represents a potential therapeutic strategy for cystic kidney disease.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780394","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":"The Association Between Diabetes and Mortality is Not Modified by Living Arrangements in Hemodialysis Patients in Japan.","authors":"Mutsumi Uesugi, Anna Tsutsui, Yoshitaka Murakami","doi":"10.34067/KID.0000000784","DOIUrl":"https://doi.org/10.34067/KID.0000000784","url":null,"abstract":"<p><strong>Background: </strong>Living arrangements, such as living alone or with a spouse, may affect mortality risk in hemodialysis patients with diabetes. This study investigated whether living arrangements modify the association between diabetes and mortality in community-dwelling hemodialysis patients in Japan.</p><p><strong>Methods: </strong>Using data from 27 outpatient dialysis units, this retrospective cohort study analysed 2799 community-dwelling hemodialysis patients (women: 33.7%) aged 40-89 years between April 2016 and March 2021. Each patient was placed into one of three categories according to living arrangements: living alone, with a spouse, or with others (excluding spouses). Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality. Interaction analyses were performed to assess the potential effect measure modification of the association between diabetes and mortality by living arrangements. The analyses were also conducted according to sex and age groups (40-64 and 65-89 years).</p><p><strong>Results: </strong>A total of 835 deaths were observed during a mean follow-up period of 3.9 years. Diabetes showed a significantly higher mortality risk (HR: 1.63, 95% CI: 1.42-1.89) in all patients. However, patients living alone did not have a significantly higher mortality risk than those living with a spouse (HR: 1.04, 95% CI: 0.87-1.24). There was no significant interaction between diabetes and living arrangements (P=0.73). Women aged 65-89 years who were living with others had a significantly higher mortality risk than those living with a spouse (HR: 1.41, 95% CI: 1.04-1.92).</p><p><strong>Conclusions: </strong>Living arrangements did not modify the association between diabetes and mortality in community-dwelling hemodialysis patients. Frequent clinic visits and lifestyle support by medical staff related to hemodialysis treatment may have facilitated diabetes management and mitigated the negative influence of social isolation, thereby reducing mortality risk.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780399","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":"Patterns in Heart Rate Variability during Hemodialysis.","authors":"Benjamin Lidgard, Nisha Bansal, Nathaniel Ashford, Leila R Zelnick, Ian H de Boer","doi":"10.34067/KID.0000000788","DOIUrl":"https://doi.org/10.34067/KID.0000000788","url":null,"abstract":"<p><strong>Background: </strong>Decreased Heart Rate Variability (HRV) is a measure of poor cardiovascular health and inability of the autonomic nervous system to respond to stress. Accumulation of uremic toxins in kidney failure, volume shifts, and clearance of uremic toxins by dialysis may impact HRV. We sought to evaluate how HRV changes over the course of hemodialysis sessions, and evaluate a novel HRV sensor.</p><p><strong>Methods: </strong>Among 22 participants treated with in-center hemodialysis, we evaluated time-domain and frequency-domain HRV metrics with a gold-standard ECG device (Schiller CARDIOVIT AT-10 Plus) and a novel fingertip sensor (EliteHRV CorSense) at five time points during 2 consecutive dialysis sessions. Changes over the session were evaluated by linear mixed models with random effect terms for participant and session. Devices were compared using correlation coefficients, Wilcoxon rank sum tests, and linear regression.</p><p><strong>Results: </strong>There were no significant changes in HRV metrics over the dialysis session (p-value for trend across ECG 0.11, across CorSense 0.58). Time-domain HRV metrics were moderately correlated between the two methods (correlation coefficient for SDNN 0.72 and for RMSSD 0.66), while frequency-domain methods were not. Linear models comparing CorSense and ECG readings suggested strong association for time-domain metrics.</p><p><strong>Conclusions: </strong>HRV metrics did not significantly change over the course of hemodialysis sessions, suggesting poor autonomic function during dialysis. A novel fingertip sensor accurately measured time-domain (but not frequency-domain) HRV metrics when compared to a gold-standard ECG device.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780397","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":"Hydroxyurea and Regression of Sickle Cell Nephropathy: Open Clinical Trial in a Pediatric Population in DR Congo.","authors":"Dieumerci Betukumesu Kabasele, Arriel Makembi Bunkete, Gloire Mbayabo, Paul Lumbala, Odio Matondo, Michel Aloni, Orly Kazadi, Tite Mikobi, Joseph Bodi Mabiala, François Kajingulu, Jean-Robert Makulo Rissassi, Ernest Sumaili, Prosper Lukusa, Jean-Lambert Gini Ehungu","doi":"10.34067/KID.0000000805","DOIUrl":"https://doi.org/10.34067/KID.0000000805","url":null,"abstract":"<p><strong>Background: </strong>Renal complications of sickle cell disease are becoming very common, and patients generally do not respond to conventional nephroprotective treatments. Among the drugs used, hydroxyurea (HU) seems to have produced good results according to some studies. This molecule has not yet been evaluated in the DR Congo for this purpose. To evaluate albuminuria and the glomerular filtration rate (GFR) after 9 months of HU treatment in a population of children with incipient sickle cell nephropathy.</p><p><strong>Methods: </strong>This was an open clinical trial involving sickle cell syndrome children under 18 years of age followed by incipient sickle cell nephropathy (glomerular hyperfiltration =GHF and/or microalbuminuria). A mean HU dose of 20 mg/kg/d was administered to each child, with quarterly clinical and biological controls. GHF (new Schwartz formula) was defined as a rate > 130 ml/min/1.73 m2 for girls and > 140 ml/min/1.73 m2 for boys; albuminuria was defined as the albuminuria/creatinuria ratio (ACR) in mg/g. The Wilcoxon and McNemar tests were used to compare the results at admission and at the 9th month of treatment.</p><p><strong>Results: </strong>In total, 30 children (mean age 8.9±4.1 years; 40% boys) whose mean fetal hemoglobin (HbF) level increased from 10±7.4 to 18.8±4.9% (p˂0.001), whose mean number of blood transfusions ranged from 7.4±6.7 to 0.1±0.3 bags/month (p˂0.001), and whose number of VOCs ranged from 1.8±1.1 to 0.2±0.4/month (p˂0.03) were included. The frequency of GHF decreased from 30% to 3.3% (p˂0.001). The mean albuminuria decreased from 122.5 ± 16.3 mg/g to 30 ± 2.4 mg/g.</p><p><strong>Conclusions: </strong>HU improved the course of sickle cell nephropathy. The mechanism of action behind this result appears to be an improvement in blood rheology.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780396","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":"Global Perspective on AKI in Chile.","authors":"Cristian Pedreros-Rosales, Gonzalo Ramírez-Guerrero, Ignacio Gacitúa-Meneses","doi":"10.34067/KID.0000000798","DOIUrl":"https://doi.org/10.34067/KID.0000000798","url":null,"abstract":"","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764160","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":"Clinical Significance of Immune Deposits and Complement System Activation in FSGS: Findings from the CureGN Study.","authors":"Yasar Caliskan, Virginie Royal, Stéphan Troyanov, Arnaud Bonnefoy, Clémence Merlen, Mark Schnitzler, John C Edwards, Krista L Lentine, Louis-Philippe Laurin","doi":"10.34067/KID.0000000787","DOIUrl":"https://doi.org/10.34067/KID.0000000787","url":null,"abstract":"<p><strong>Background: </strong>The interplay between complement activation and the immune response in focal segmental glomerulosclerosis (FSGS) warrants further investigation. We investigated the association of glomerular C3 and IgM immunostaining with FSGS disease activity, complement system activation, chronicity on kidney biopsy, initial and follow-up clinical data in the Cure Glomerulopathy Network (CureGN) FSGS cohort.</p><p><strong>Methods: </strong>Data for FSGS patients with available pathology assessment from the CureGN cohort were reviewed. We tested associations between glomerular immunoglobulins and C3 staining intensity by immunofluorescence with the Columbia classification, the urinary membrane attack complex (sC5b9) level, proteinuria, and time to a composite outcome, defined by end stage kidney disease (ESKD) or a 40% decline in eGFR. Urinary sC5b9 levels, expressed as ratios to creatinine (sC5b9CR) and to protein (C5b9uPR), were also examined.</p><p><strong>Results: </strong>The study cohort comprised 175 FSGS patients, including 63 (36%) incident subjects enrolled within 6 months of pathology review. Glomerular IgM, C3 and IgG deposits were found in 88 (50%), 48 (27.4%) and 27 (15.4%) patients, respectively. C3 deposition was correlated with global sclerosis (r=0.27, p<0.001), tubular microcystic changes (r=0.19, p<0.01), interstitial fibrosis tubular atrophy (IFTA) (r=0.17, p=0.03), interstitial inflammation (r=0.17, p=0.03), and tip lesion (r=-0.16, p=0.04). In incident patients, C5b9uPR correlated with total segmental sclerosis (r=0.35, p<0.01), IF (r=0.33, p=0.01), IFTA (r=0.35, p<0.01), and interstitial inflammation (r=0.29, p=0.03). Only C5b9uPR [HR=1.64 (95%CI 1.03-2.60, p=0.03)] and age at enrollment [HR=1.01 (95%CI 1.00-1.03, p=0.02)] were significantly associated with the composite outcome in the adjusted Cox survival models.</p><p><strong>Conclusions: </strong>C5b9uPR is emerging as a significant biomarker for FSGS progression, reflecting the complex interplay between complement activation, inflammation, and kidney injury. The evidence suggests that elevated C5b9uPR levels are associated with poor kidney outcomes and may serve as a valuable tool in the non-invasive assessment of kidney fibrosis and disease progression.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764158","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":"Intradialytic Parenteral Nutrition During In-Center Hemodialysis of Patients Leads to Increase in Albumin Without Compromising Safety: Retrospective Analysis.","authors":"Maiya Slusser-Hogan, Jamie Haight, Lori Gabriel, Mark A Hardy, Karin Hehenberger","doi":"10.34067/KID.0000000789","DOIUrl":"https://doi.org/10.34067/KID.0000000789","url":null,"abstract":"<p><strong>Background: </strong>Albumin is an established survival surrogate in dialysis. We evaluated the effect of intradialytic parenteral nutrition (IDPN) on albumin levels in patients with end-stage renal disease (ESRD) undergoing in-center hemodialysis (ICHD) and determined characteristics associated with response to IDPN treatment.</p><p><strong>Methods: </strong>We conducted a 5-year (05/2018 - 04/2023) retrospective chart review of 2,270 ICHD patients from 1039 Dialysis Centers, in 43 states and D.C., who received concurrent IDPN treatment 3 times per week. Patients were ≥18y (mean 69.1y) with albumin levels <4.0 g/dl (mean 3.11g/dl) and were on HD for more than 6 mos (mean 3.7 years). Other criteria included unintentional weight loss (≥5%/3mo) and/or BMI below 20kg/m2. The co-primary endpoints included mean change in albumin levels from baseline to month 6 of IDPN therapy and percentage of patients with a clinically significant change in albumin levels, defined as ≥0.2 g/d with a p<0.05. Each patient studied was their own control. We used Kaplan-Meier curves to evaluate the time to positive IDPN response. Two-sample t-tests for continuous variables and Chi-square tests for categorical variables were used to determine if certain defined patient characteristics were associated with a positive response to IDPN therapy.</p><p><strong>Results: </strong>1,946 eligible patients consented to being evaluated. Baseline demographics (Table 1) include: 50.9% female and 49.1% male with a mean albumin of 3.11g/dL. Evaluable data at six months were available for 73% of patients. Mean change in albumin levels from baseline to 6 months after initiation of IDPN therapy was 0.330 g/dL; 82.0% of patients achieved ≥0.2-g/dL increase in albumin level within those six months. Younger age and lower baseline albumin levels were significantly and independently associated with a higher and more rapid significant rise, p <0.05, in albumin levels. While receiving IDPN, fewer than 8% of patients reported minimal and treatable side effects.</p><p><strong>Conclusion: </strong>IDPN is a safe and effective therapy resulting in clinically significant improvement in serum albumin levels. Further research on associated outcomes and QoL data is needed.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764162","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":"Homocitrulline is Associated with Cardiovascular Outcomes in Non-Dialysis Patients with CKD.","authors":"Solène M Laville, Stéphane Jaisson, Philippe Gillery, Anaïs Okwieka, Natalia Alencar de Pinho, Christian Combe, Nicolas Mansencal, Ziad A Massy, Sophie Liabeuf","doi":"10.34067/KID.0000000797","DOIUrl":"https://doi.org/10.34067/KID.0000000797","url":null,"abstract":"<p><strong>Background: </strong>Protein carbamylation contributes to an increase in the cardiovascular risk in certain patient populations (e.g. in patients with chronic kidney disease (CKD) because of elevated urea concentrations). Homocitrulline (HCit) is a biomarker of overall protein carbamylation. In a study of a large cohort of non-dialysis patients with a confirmed diagnosis of CKD and an estimated glomerular filtration rate (eGFR) <60mL/min/1.73m2, we sought to determine whether the serum HCit concentration was associated with adverse cardiovascular outcomes and all-cause mortality.</p><p><strong>Methods: </strong>CKD-REIN is a prospective cohort of CKD patients with an eGFR<60mL/min/1.73m2. The baseline serum HCit concentration was centrally measured. The 2,195 patients included in the analysis were divided into tertiles (T) groups according to the baseline HCit concentration (T1<292, T2=[292-429], and T3≥430 µmol/mol lysine). Adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) for the first major adverse cardiovascular event (MACE) and death before kidney replacement therapy (KRT).</p><p><strong>Results: </strong>Among the 2,195 included patients, the median age was 68, and the mean eGFR was 34.6 mL/min/1.73m2. The median [IQR] serum HCit was 352[266-481] µmol/mol lysine. The HCit concentration was correlated with the eGFR (r=-0.57) and the urea concentrations (r=0.73). In an adjusted linear regression model, the HCit concentration was independently and positively associated with age, eGFR decrease, urea, anemia, baseline prescription of diuretics, and negatively associated with male sex and an elevated urinary albumin-to-creatinine ratio. The adjusted HR[95%CI] for MACEs as a function of the baseline HCit concentration was 1.32[0.96-1.84] for T2 and 1.63[1.16-2.30] for T3, compared to T1. The risk of death before KRT as a function of the baseline serum HCit concentration was 2.09[1.45-3.03] for T3 and 1.48[1.04-2.11] for T2, compared to T1.</p><p><strong>Conclusions: </strong>Our analysis of a large cohort of patients with CKD demonstrated that the serum HCit concentration was associated with a greater likelihood of a MACE and death. To confirm causality, further studies of therapeutic interventions for preventing or reducing carbamylation are now warranted.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764161","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":"Effects of SGLT2 Inhibitors on Modulating Protein-Bound Uremic Toxins and Gut Microbiota in Pre-Dialysis CKD Patients: A Matched Case-Control Study.","authors":"Cheng-Kai Hsu, Lun-Ching Chang, Yih-Ting Chen, Chun-Yu Chen, Heng-Rong Hsu, Shi Bai, Chin-Chan Lee, Hansraj Jangir, Chiao-Yin Sun, Shih-Chi Su, I-Wen Wu","doi":"10.34067/KID.0000000792","DOIUrl":"https://doi.org/10.34067/KID.0000000792","url":null,"abstract":"<p><strong>Background: </strong>The intricate interplay between chronic kidney disease (CKD) and intestinal microbiota has gained increasing attention, with gut dysbiosis being implicated in uremic toxin accumulation and CKD progression. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are now transforming CKD management but pose uncertain effects on shaping gut microbiota. This study aimed to elucidate the impact of SGLT2 inhibitors on perturbations of gut microbial composition and metabolic responses in CKD patients.</p><p><strong>Methods: </strong>Analysis of fecal microbiota and targeted profiling of serum short-chain fatty acids (SCFAs) and gut-derived uremic toxins were conducted in a matched case-control study, including 60 CKD patients (treated: n=30; untreated: n=30) and 30 non-CKD controls.</p><p><strong>Results: </strong>Gut microbial composition differed significantly among three study groups. CKD patients receiving SGLT2 inhibitors exhibited distinctive taxonomic profiles, such as enrichment of Bacteroides stercoris and Bacteroides coprocola. Surveys of metabolomic profiles revealed a reduction of two uremic solutes, indoxyl sulfate (IS) and p-cresyl sulfate (pCS), and several SCFAs (formic, acetic, propionic, valeric, and 2-methylbutanoic acid) in SGLT2 inhibitor-treated CKD patients. Co-occurrence analysis demonstrated a set of intestinal microbes that is positively or negatively correlated with the levels of pCS, and the abundance of these pCS-associated intestinal microorganisms was correlated with the levels of IS and isovaleric acids in the same and opposite direction, respectively. Further functional prediction indicated attenuated pathways related to protein and carbohydrate metabolism.</p><p><strong>Conclusions: </strong>Treatment with SGLT2 inhibitors in CKD patients is associated with distinct gut microbial composition and metabolite profiles, suggesting potential modulation of gut dysbiosis and metabolic pathways. Further studies are warranted to elucidate the clinical implications of these findings in CKD management.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764159","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}