Pub Date : 2024-01-31DOI: 10.1101/2024.01.31.24302046
Carl Mikael Oberg
Introduction: Larger fill volumes in peritoneal dialysis (PD) typically improve small solute clearance and water removal, and vice versa – but the relationship between intra-peritoneal volume and the capacities for solute and water transport in PD has been little studied. Here, it is proposed that this relative relationship is described by a simple ratio (Volumenew/Volumeold)2/3 up to a critical break-point volume, beyond which further volume increase is less beneficial in terms of transport. Method: To scrutinize this hypothesis, experiments were conducted in a rat model of PD alongside a retrospective analysis of clinical data from a prior study. Rats underwent PD with either three consecutive fills of 8+8+8 mL (n=10) or 12+12+12 mL (n=10), with 45-minute dwell time intervals. This approach yielded sixty estimations of water and solute transport, characterized by osmotic conductance to glucose (OCG) and solute diffusion capacities, respectively. Results: Comparative analysis of the predictive efficacy of the two models – the simple ratio versus the break-point model – was performed using Monte Carlo cross-validation. The break-point model emerged as a superior predictor for both water and solute transport, demonstrating its capability to characterize both experimental and clinical data. Conclusion: The present analysis indicates that relatively simple calculations can be used to approximate clinical effects on transport when prescribing a lower or higher fill volume to patients on PD.
{"title":"Relationship between fill volume and transport in peritoneal dialysis","authors":"Carl Mikael Oberg","doi":"10.1101/2024.01.31.24302046","DOIUrl":"https://doi.org/10.1101/2024.01.31.24302046","url":null,"abstract":"<strong>Introduction:</strong> Larger fill volumes in peritoneal dialysis (PD) typically improve small solute clearance and water removal, and <em>vice versa</em> – but the relationship between intra-peritoneal volume and the capacities for solute and water transport in PD has been little studied. Here, it is proposed that this relative relationship is described by a simple ratio (Volume<sub>new</sub>/Volume<sub>old</sub>)<sup>2/3</sup> up to a critical break-point volume, beyond which further volume increase is less beneficial in terms of transport.\u0000<strong>Method:</strong> To scrutinize this hypothesis, experiments were conducted in a rat model of PD alongside a retrospective analysis of clinical data from a prior study. Rats underwent PD with either three consecutive fills of 8+8+8 mL (n=10) or 12+12+12 mL (n=10), with 45-minute dwell time intervals. This approach yielded sixty estimations of water and solute transport, characterized by osmotic conductance to glucose (OCG) and solute diffusion capacities, respectively.\u0000<strong>Results:</strong> Comparative analysis of the predictive efficacy of the two models – the simple ratio versus the break-point model – was performed using Monte Carlo cross-validation. The break-point model emerged as a superior predictor for both water and solute transport, demonstrating its capability to characterize both experimental and clinical data.\u0000<strong>Conclusion:</strong> The present analysis indicates that relatively simple calculations can be used to approximate clinical effects on transport when prescribing a lower or higher fill volume to patients on PD.","PeriodicalId":501513,"journal":{"name":"medRxiv - Nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139657021","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 : 2024-01-28DOI: 10.1101/2024.01.26.24301848
John J Sim, Yu-Hsiang Shu, Simran K. Bhandari, Qiaoling Chen, Teresa N. Harrison, Min Young Lee, Mercedes A. Munis, Kerresa Morrissette, Shirin Sundar, Kristin Pareja, Ali Nourbakhsh, Cynthia J. Willey
Background Autosomal dominant polycystic kidney disease (ADPKD) is a genetic kidney disease with high phenotypic variability. Insights into ADPKD progression could lead to earlier detection and management prior to end stage kidney disease (ESKD). We sought to identify patients with rapid decline (RD) in kidney function and to determine clinical factors associated with RD using a data-driven approach. Methods A retrospective cohort study was performed among patients with incident ADPKD (1/1/2002-12/31/2018). Latent class mixed models were used to identify RD patients using rapidly declining eGFR trajectories over time. Predictors of RD were selected based on agreements among feature selection methods, including logistic, regularized, and random forest modeling. The final model was built on the selected predictors and clinically relevant covariates. Results Among 1,744 patients with incident ADPKD, 125 (7%) were identified as RD. Feature selection included 42 clinical measurements for adaptation with multiple imputations; mean (SD) eGFR was 85.2 (47.3) and 72.9 (34.4) in the RD and non-RD groups, respectively. Multiple imputed datasets identified variables as important features to distinguish RD and non-RD groups with the final prediction model determined as a balance between area under the curve (AUC) and clinical relevance which included 6 predictors: age, sex, hypertension, cerebrovascular disease, hemoglobin, and proteinuria. Results showed 72%-sensitivity, 70%-specificity, 70%-accuracy, and 0.77-AUC in identifying RD. 5-year ESKD rates were 38% and 7% among RD and non-RD groups, respectively. Conclusion Using real-world routine clinical data among patients with incident ADPKD, we observed that six variables highly predicted RD in kidney function.
{"title":"Data Driven Approach to Characterize Rapid Decline in Autosomal Dominant Polycystic Kidney Disease","authors":"John J Sim, Yu-Hsiang Shu, Simran K. Bhandari, Qiaoling Chen, Teresa N. Harrison, Min Young Lee, Mercedes A. Munis, Kerresa Morrissette, Shirin Sundar, Kristin Pareja, Ali Nourbakhsh, Cynthia J. Willey","doi":"10.1101/2024.01.26.24301848","DOIUrl":"https://doi.org/10.1101/2024.01.26.24301848","url":null,"abstract":"Background\u0000Autosomal dominant polycystic kidney disease (ADPKD) is a genetic kidney disease with high phenotypic variability. Insights into ADPKD progression could lead to earlier detection and management prior to end stage kidney disease (ESKD). We sought to identify patients with rapid decline (RD) in kidney function and to determine clinical factors associated with RD using a data-driven approach. Methods A retrospective cohort study was performed among patients with incident ADPKD (1/1/2002-12/31/2018). Latent class mixed models were used to identify RD patients using rapidly declining eGFR trajectories over time. Predictors of RD were selected based on agreements among feature selection methods, including logistic, regularized, and random forest modeling. The final model was built on the selected predictors and clinically relevant covariates. Results Among 1,744 patients with incident ADPKD, 125 (7%) were identified as RD. Feature selection included 42 clinical measurements for adaptation with multiple imputations; mean (SD) eGFR was 85.2 (47.3) and 72.9 (34.4) in the RD and non-RD groups, respectively. Multiple imputed datasets identified variables as important features to distinguish RD and non-RD groups with the final prediction model determined as a balance between area under the curve (AUC) and clinical relevance which included 6 predictors: age, sex, hypertension, cerebrovascular disease, hemoglobin, and proteinuria. Results showed 72%-sensitivity, 70%-specificity, 70%-accuracy, and 0.77-AUC in identifying RD. 5-year ESKD rates were 38% and 7% among RD and non-RD groups, respectively. Conclusion Using real-world routine clinical data among patients with incident ADPKD, we observed that six variables highly predicted RD in kidney function.","PeriodicalId":501513,"journal":{"name":"medRxiv - Nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139584829","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}
Purpose Moderate-intensity exercise has beneficial effects for individuals with CKD. However, it is unclear whether intermittent exercise (IE) has a different effect on renal haemodynamics compared to continuous exercise (CE). This study aimed to compare the effects of intermittent or continuous exercise on renal haemodynamics and renal injury during moderate-intensity exercise. Methods Ten males underwent IE or CE to consider the effect of exercise on renal haemodynamics during moderate-intensity exercise. Renal haemodynamic assessment and blood-sampling were conducted before exercise (pre) and immediately (post 0), 30-min (post 30), and 60-min (post 60) after exercise. Urine-sampling was conducted in pre, post 0 and post 60. Results There was no condition-by-time interaction (p = 0.073), condition (p = 0.696), or time (p = 0.433) effects regarding renal blood flow. There was a condition-by-time interaction effect regarding noradrenaline concentrations (p = 0.037). Moreover, both conditions significantly increased noradrenaline concentration at post 0 (IE: p = 0.003, CE: p < 0.001) and remained significantly higher in post 30 (p < 0.001) and post 60 (p < 0.001). Significant difference was found in noradrenaline concentrations at post 0 when comparing IE and CE (399 ± 119 vs. 552 ± 224 pg/ml, p = 0.037). Urinary neutrophil gelatinase-associated lipocalin concentrations increased at post 60 (p = 0.009), but none of them exceeded the cutoff values for the definition of renal damage. Other renal injury biomarkers showed a similar pattern. Conclusion These findings suggest that IE has a similar effect on renal haemodynamics and function, and AKI biomarkers compared to CE.
{"title":"The effects of intermittent or continuous exercise on renal haemodynamics during moderate-intensity exercise","authors":"Shotaro Kawakami, Tetsuhiko Yasuno, Saki Kawakami, Ai Ito, Kanta Fujimi, Takuro Matsuda, Shihoko Nakashima, Kosuke Masutani, Yoshinari Uehara, Yasuki Higaki, Ryoma Michishita","doi":"10.1101/2024.01.23.24301695","DOIUrl":"https://doi.org/10.1101/2024.01.23.24301695","url":null,"abstract":"Purpose Moderate-intensity exercise has beneficial effects for individuals with CKD. However, it is unclear whether intermittent exercise (IE) has a different effect on renal haemodynamics compared to continuous exercise (CE). This study aimed to compare the effects of intermittent or continuous exercise on renal haemodynamics and renal injury during moderate-intensity exercise.\u0000Methods Ten males underwent IE or CE to consider the effect of exercise on renal haemodynamics during moderate-intensity exercise. Renal haemodynamic assessment and blood-sampling were conducted before exercise (pre) and immediately (post 0), 30-min (post 30), and 60-min (post 60) after exercise. Urine-sampling was conducted in pre, post 0 and post 60.\u0000Results There was no condition-by-time interaction (p = 0.073), condition (p = 0.696), or time (p = 0.433) effects regarding renal blood flow. There was a condition-by-time interaction effect regarding noradrenaline concentrations (p = 0.037). Moreover, both conditions significantly increased noradrenaline concentration at post 0 (IE: p = 0.003, CE: p < 0.001) and remained significantly higher in post 30 (p < 0.001) and post 60 (p < 0.001). Significant difference was found in noradrenaline concentrations at post 0 when comparing IE and CE (399 ± 119 vs. 552 ± 224 pg/ml, p = 0.037). Urinary neutrophil gelatinase-associated lipocalin concentrations increased at post 60 (p = 0.009), but none of them exceeded the cutoff values for the definition of renal damage. Other renal injury biomarkers showed a similar pattern.\u0000Conclusion These findings suggest that IE has a similar effect on renal haemodynamics and function, and AKI biomarkers compared to CE.","PeriodicalId":501513,"journal":{"name":"medRxiv - Nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139584839","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}
Background and hypothesis Sarcopenia is common in patients undergoing maintenance haemodialysis (MHD); however, the current diagnostic support tools for sarcopenia are difficult to implement in dialysis clinics. This study aimed to develop a clinically friendly screening tool to predict sarcopenia using ubiquitous clinical data.
{"title":"Development and external validation of a practical diagnostic support tool, ‘ABC2-Screener’, to predict sarcopenia among patients on maintenance haemodialysis: A multicentre cross-sectional study","authors":"Masatoshi Matsunami, Tetsuro Aita, Tsukasa Kamitani, Yu Munakata, Atsuro Kawaji, Hiroshi Kuji, Tomo Suzuki, Noriaki Kurita","doi":"10.1101/2024.01.17.24301264","DOIUrl":"https://doi.org/10.1101/2024.01.17.24301264","url":null,"abstract":"<strong>Background and hypothesis</strong> Sarcopenia is common in patients undergoing maintenance haemodialysis (MHD); however, the current diagnostic support tools for sarcopenia are difficult to implement in dialysis clinics. This study aimed to develop a clinically friendly screening tool to predict sarcopenia using ubiquitous clinical data.","PeriodicalId":501513,"journal":{"name":"medRxiv - Nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139507575","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 : 2024-01-17DOI: 10.1101/2024.01.16.24301361
Dawson Dean
Guidelines recommend avoiding unnecessary laboratory tests to minimize risks of anemia in hospitalized patients as well as reduce costs. Avoiding routine labs, however, may introduce new risks of missing conditions that do not have physical exam or history findings, such as Acute Kidney Injury. This study analyzes retrospective data for routine laboratory results and simulates different strategies for skipping labs. It estimates potential benefits from avoiding iatrogenic anemia as well as costs from increased risk of Acute Kidney Injury. In a simplified estimate of pure dollar costs, the costs of daily labs appear to significantly outweigh the costs of missing Acute Kidney Injury, but there are costs to skipping routine labs.
{"title":"Routine Labs in Hospital Patients: Iatrogenic Anemia and Missed Acute Kidney Injury","authors":"Dawson Dean","doi":"10.1101/2024.01.16.24301361","DOIUrl":"https://doi.org/10.1101/2024.01.16.24301361","url":null,"abstract":"Guidelines recommend avoiding unnecessary laboratory tests to minimize risks of anemia in hospitalized patients as well as reduce costs. Avoiding routine labs, however, may introduce new risks of missing conditions that do not have physical exam or history findings, such as Acute Kidney Injury. This study analyzes retrospective data for routine laboratory results and simulates different strategies for skipping labs. It estimates potential benefits from avoiding iatrogenic anemia as well as costs from increased risk of Acute Kidney Injury. In a simplified estimate of pure dollar costs, the costs of daily labs appear to significantly outweigh the costs of missing Acute Kidney Injury, but there are costs to skipping routine labs.","PeriodicalId":501513,"journal":{"name":"medRxiv - Nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139507711","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 : 2024-01-15DOI: 10.1101/2024.01.13.24301272
Carlos Augusto Pereira de Almeida, Marcia Fernanda Arantes de Oliveira, Alexandre Macedo Teixeira, Carla Paulina Sandoval Cabrera, Igor Smolentzov, Bernardo Vergara Reichert, Paulo Ricardo Gessolo Lins, Camila Eleuterio Rodrigues, Victor Faria Seabra, Lucia Andrade
The objective of this study was to evaluate two different criteria for deciding when KRT should be initiated in patients with COVID-19-related AKI, as well as to determine the impact of the timing of KRT, as defined by each criterion, on in-hospital mortality among such patients. This was a retrospective study involving 512 adult patients admitted to the ICU. All participants had laboratory-confirmed COVID-19 and a confirmed diagnosis of AKI. The potential predictors were the determination of the timing of KRT based on a temporal criterion (days since hospital admission) and that based on a serum creatinine cutoff criterion. Covariates included age, sex, and the SOFA score, as well as the need for mechanical ventilation and vasopressors. The main outcome measure was in-hospital mortality. We evaluated 512 patients, of whom 69.1% were men. The median age was 64 years. Of the 512 patients, 76.6% required dialysis after admission. The overall in-hospital mortality rate was 72.5%. When the timing of KRT was determined by the temporal criterion, the risk of in-hospital mortality was significantly higher for delayed KRT than for timely KRT—84% higher in the univariate analysis (OR=1.84, 95%, [CI]: 1.10-3.09) and 140% higher after adjustment for age, sex, and SOFA score (OR=2.40, 95% CI: 1.36-4.24). When it was determined by the creatinine cutoff criterion, there was no such difference between high and low creatinine at KRT initiation. In patients with COVID-19-related AKI, earlier KRT appears to be associated with lower in-hospital mortality.
{"title":"Kidney Replacement Therapy in COVID-19-Related Acute Kidney Injury: the Importance of Timing","authors":"Carlos Augusto Pereira de Almeida, Marcia Fernanda Arantes de Oliveira, Alexandre Macedo Teixeira, Carla Paulina Sandoval Cabrera, Igor Smolentzov, Bernardo Vergara Reichert, Paulo Ricardo Gessolo Lins, Camila Eleuterio Rodrigues, Victor Faria Seabra, Lucia Andrade","doi":"10.1101/2024.01.13.24301272","DOIUrl":"https://doi.org/10.1101/2024.01.13.24301272","url":null,"abstract":"The objective of this study was to evaluate two different criteria for deciding when KRT should be initiated in patients with COVID-19-related AKI, as well as to determine the impact of the timing of KRT, as defined by each criterion, on in-hospital mortality among such patients. This was a retrospective study involving 512 adult patients admitted to the ICU. All participants had laboratory-confirmed COVID-19 and a confirmed diagnosis of AKI. The potential predictors were the determination of the timing of KRT based on a temporal criterion (days since hospital admission) and that based on a serum creatinine cutoff criterion. Covariates included age, sex, and the SOFA score, as well as the need for mechanical ventilation and vasopressors. The main outcome measure was in-hospital mortality. We evaluated 512 patients, of whom 69.1% were men. The median age was 64 years. Of the 512 patients, 76.6% required dialysis after admission. The overall in-hospital mortality rate was 72.5%. When the timing of KRT was determined by the temporal criterion, the risk of in-hospital mortality was significantly higher for delayed KRT than for timely KRT—84% higher in the univariate analysis (OR=1.84, 95%, [CI]: 1.10-3.09) and 140% higher after adjustment for age, sex, and SOFA score (OR=2.40, 95% CI: 1.36-4.24). When it was determined by the creatinine cutoff criterion, there was no such difference between high and low creatinine at KRT initiation. In patients with COVID-19-related AKI, earlier KRT appears to be associated with lower in-hospital mortality.","PeriodicalId":501513,"journal":{"name":"medRxiv - Nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139482873","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 : 2023-12-19DOI: 10.1101/2023.12.19.23300205
WILLIAM SUCIANGTO, Haerani Rasyid, Anastasya Angelica Vicente, Winny Suciangto
Abstract Background: Chronic kidney disease (CKD) is a major global health problem. Hyperphosphatemia is frequent in CKD and a reason for increased morbidity and mortality as it generates hyperparathyroidism, high fibroblast growth factor 23 (FGF23), and hypocalcemia. Available hyperphosphatemia therapies still have limitations, including risk of metal overload, cardiovascular calcification, and systemic adverse effects (AEs). Tenapanor is a new hyperphosphatemia treatment in CKD with sodium-hydrogen exchanger isoform 3 (NHE3) inhibition mechanism and low systemic AEs. Objectives: Discovering the effectivity and safety of tenapanor as hyperphosphatemia management in CKD. Method: Literature searching is performed by using pubmed and science direct with tenapanor, chronic kidney disease, and hyperphosphatemia as keywords. The literatures were selected using PRISMA algorithm version 2020. Literature was screened based on Population, Intervention, Comparison, and Outcome (PICO) criteria which are: CKD patients requiring dialysis as population, tenapanor or its combination with dialysis or phosphate binders as intervention, placebo or other phosphate binders without tenapanor as comparison, and serum phosphate, safety profile, and other pleiotropic benefits related to hyperphosphatemia management as the outcome. The included studies then assessed for risk of bias and qualitatively reviewed. Outcome: Tenapanor was able to reduce serum phosphate, generally in a dose-dependent manner. Tenapanor also suppressed FGF23 and parathyroid hormone, probably due to decreased serum phosphate. The frequent AEs was transient mild-to-moderate diarrhea in a dose-dependent manner. Tenapanor was generally well-tolerated with low systemic AEs due to its non-calcium, metal-free, and low-absorbed properties. Conclusion: Tenapanor is an effective and safe option for hyperphosphatemia management in CKD.
{"title":"Effectivity and Safety Profile of Tenapanor, a Sodium-Hydrogen Exchanger Isoform 3 Inhibitor, as an Innovative Treatment for Hyperphosphatemia in Chronic Kidney Disease, a Systematic Review of Clinical Studies","authors":"WILLIAM SUCIANGTO, Haerani Rasyid, Anastasya Angelica Vicente, Winny Suciangto","doi":"10.1101/2023.12.19.23300205","DOIUrl":"https://doi.org/10.1101/2023.12.19.23300205","url":null,"abstract":"Abstract\u0000Background: Chronic kidney disease (CKD) is a major global health problem. Hyperphosphatemia is frequent in CKD and a reason for increased morbidity and mortality as it generates hyperparathyroidism, high fibroblast growth factor 23 (FGF23), and hypocalcemia. Available hyperphosphatemia therapies still have limitations, including risk of metal overload, cardiovascular calcification, and systemic adverse effects (AEs). Tenapanor is a new hyperphosphatemia treatment in CKD with sodium-hydrogen exchanger isoform 3 (NHE3) inhibition mechanism and low systemic AEs. Objectives: Discovering the effectivity and safety of tenapanor as hyperphosphatemia management in CKD. Method: Literature searching is performed by using pubmed and science direct with tenapanor, chronic kidney disease, and hyperphosphatemia as keywords. The literatures were selected using PRISMA algorithm version 2020. Literature was screened based on Population, Intervention, Comparison, and Outcome (PICO) criteria which are: CKD patients requiring dialysis as population, tenapanor or its combination with dialysis or phosphate binders as intervention, placebo or other phosphate binders without tenapanor as comparison, and serum phosphate, safety profile, and other pleiotropic benefits related to hyperphosphatemia management as the outcome. The included studies then assessed for risk of bias and qualitatively reviewed. Outcome: Tenapanor was able to reduce serum phosphate, generally in a dose-dependent manner. Tenapanor also suppressed FGF23 and parathyroid hormone, probably due to decreased serum phosphate. The frequent AEs was transient mild-to-moderate diarrhea in a dose-dependent manner. Tenapanor was generally well-tolerated with low systemic AEs due to its non-calcium, metal-free, and low-absorbed properties. Conclusion: Tenapanor is an effective and safe option for hyperphosphatemia management in CKD.","PeriodicalId":501513,"journal":{"name":"medRxiv - Nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138818523","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 : 2023-12-18DOI: 10.1101/2023.12.15.23300050
Armin Ahmadi, Jorge Gamboa, Jennifer E. Norman, Byambaa Enkhmaa, Madelynn Tucker, Brian J. Bennett, Leila R. Zelnick, Sili Fan, Lars F. Berglund, Talat Alp Ikizler, Ian H. de Boer, Bethany P. Cummings, Baback Roshanravan
Background: Incretins are regulators of insulin secretion and glucose homeostasis that are metabolized by dipeptidyl peptidase-4 (DPP-4). Moderate-severe CKD may modify incretin release, metabolism, or response. Methods: We performed 2-hour oral glucose tolerance testing (OGTT) in 59 people with non-diabetic CKD (eGFR<60 ml/min per 1.73 m2) and 39 matched controls. We measured total (tAUC) and incremental (iAUC) area under the curve of plasma total glucagon-like peptide-1 (GLP-1) and total glucose-dependent insulinotropic polypeptide (GIP). Fasting DPP-4 levels and activity were measured. Linear regression was used to adjust for demographic, body composition, and lifestyle factors. Results: Mean eGFR was 38 (13) and 89 (17)ml/min per 1.73 m2 in CKD and controls. GLP-1 iAUC and GIP iAUC were higher in CKD than controls with a mean of 1531 (1452) versus 1364 (1484) pMxmin, and 62370 (33453) versus 42365 (25061) pgxmin/ml, respectively. After adjustment, CKD was associated with 15271 pMxmin/ml greater GIP iAUC (95% CI 387, 30154) compared to controls. Adjustment for covariates attenuated associations of CKD with higher GLP-1 iAUC (adjusted difference, 122, 95% CI -619, 864). Plasma glucagon levels were higher at 30 minutes (mean difference, 1.6, 95% CI 0.3, 2.8 mg/dl) and 120 minutes (mean difference, 0.84, 95% CI 0.2, 1.5 mg/dl) in CKD compared to controls. There were no differences in insulin levels or plasma DPP-4 activity or levels between groups. Conclusion Incretin response to oral glucose is preserved or augmented in moderate-severe CKD, without apparent differences in circulating DPP-4 concentration or activity. However, neither insulin secretion nor glucagon suppression are enhanced.
{"title":"Impaired incretin homeostasis in non-diabetic moderate-severe chronic kidney disease","authors":"Armin Ahmadi, Jorge Gamboa, Jennifer E. Norman, Byambaa Enkhmaa, Madelynn Tucker, Brian J. Bennett, Leila R. Zelnick, Sili Fan, Lars F. Berglund, Talat Alp Ikizler, Ian H. de Boer, Bethany P. Cummings, Baback Roshanravan","doi":"10.1101/2023.12.15.23300050","DOIUrl":"https://doi.org/10.1101/2023.12.15.23300050","url":null,"abstract":"Background: Incretins are regulators of insulin secretion and glucose homeostasis that are metabolized by dipeptidyl peptidase-4 (DPP-4). Moderate-severe CKD may modify incretin release, metabolism, or response.\u0000Methods: We performed 2-hour oral glucose tolerance testing (OGTT) in 59 people with non-diabetic CKD (eGFR<60 ml/min per 1.73 m2) and 39 matched controls. We measured total (tAUC) and incremental (iAUC) area under the curve of plasma total glucagon-like peptide-1 (GLP-1) and total glucose-dependent insulinotropic polypeptide (GIP). Fasting DPP-4 levels and activity were measured. Linear regression was used to adjust for demographic, body composition, and lifestyle factors. Results: Mean eGFR was 38 (13) and 89 (17)ml/min per 1.73 m2 in CKD and controls. GLP-1 iAUC and GIP iAUC were higher in CKD than controls with a mean of 1531 (1452) versus 1364 (1484) pMxmin, and 62370 (33453) versus 42365 (25061) pgxmin/ml, respectively. After adjustment, CKD was associated with 15271 pMxmin/ml greater GIP iAUC (95% CI 387, 30154) compared to controls. Adjustment for covariates attenuated associations of CKD with higher GLP-1 iAUC (adjusted difference, 122, 95% CI -619, 864). Plasma glucagon levels were higher at 30 minutes (mean difference, 1.6, 95% CI 0.3, 2.8 mg/dl) and 120 minutes (mean difference, 0.84, 95% CI 0.2, 1.5 mg/dl) in CKD compared to controls. There were no differences in insulin levels or plasma DPP-4 activity or levels between groups. Conclusion Incretin response to oral glucose is preserved or augmented in moderate-severe CKD, without apparent differences in circulating DPP-4 concentration or activity. However, neither insulin secretion nor glucagon suppression are enhanced.","PeriodicalId":501513,"journal":{"name":"medRxiv - Nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138742221","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}
Rationale & Objective Person-centered care (PCC), which incorporates patients’ preferences and values not only for medical care but also for their life, in decision making has been proposed for promoting advance care planning (ACP) among patients with kidney failure.
{"title":"Association Between Person-Centered Care Quality and Advance Care Planning Participation in Patients Undergoing Hemodialysis: A Multicenter Cross-Sectional Study","authors":"Yusuke Kanakubo, Noriaki Kurita, Mamiko Ukai, Tetsuro Aita, Ryohei Inanaga, Atsuro Kawaji, Takumi Toishi, Masatoshi Matsunami, Yu Munakata, Tomo Suzuki, Tadao Okada","doi":"10.1101/2023.12.15.23300045","DOIUrl":"https://doi.org/10.1101/2023.12.15.23300045","url":null,"abstract":"<strong>Rationale & Objective</strong> Person-centered care (PCC), which incorporates patients’ preferences and values not only for medical care but also for their life, in decision making has been proposed for promoting advance care planning (ACP) among patients with kidney failure.","PeriodicalId":501513,"journal":{"name":"medRxiv - Nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138818618","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 : 2023-12-17DOI: 10.1101/2023.12.16.23300066
Xinfang Tang, Hanyang Qian, Ming Zeng, Hui Huang, Shijiu Lu, Jing Wang, Fan Li, Anning Bian, Xiaoxue Ye, Guang Yang, Kefan Ma, Changying Xing, Yi Xu, Ningning Wang
Introduction The Agatston coronary artery calcification score (CACS) is an assessment index for coronary artery calcification (CAC). This study aims to explore the characteristics of CAC in end-stage kidney disease (ESKD) patients and establish a predictive model to assess the risk of severe CAC in patients.
{"title":"Predictive Model for Severe Coronary Artery Calcification in ESKD Patients","authors":"Xinfang Tang, Hanyang Qian, Ming Zeng, Hui Huang, Shijiu Lu, Jing Wang, Fan Li, Anning Bian, Xiaoxue Ye, Guang Yang, Kefan Ma, Changying Xing, Yi Xu, Ningning Wang","doi":"10.1101/2023.12.16.23300066","DOIUrl":"https://doi.org/10.1101/2023.12.16.23300066","url":null,"abstract":"<strong>Introduction</strong> The Agatston coronary artery calcification score (CACS) is an assessment index for coronary artery calcification (CAC). This study aims to explore the characteristics of CAC in end-stage kidney disease (ESKD) patients and establish a predictive model to assess the risk of severe CAC in patients.","PeriodicalId":501513,"journal":{"name":"medRxiv - Nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138818437","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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