Pub Date : 2024-07-18DOI: 10.1016/j.kint.2024.05.022
Acute kidney injury is still associated with high morbidity and mortality. Reichardt et al. investigated DNA-binding protein-A (Ybx3) in acute kidney injury induced by ischemia-reperfusion injury and found that mice lacking Ybx3 have altered mitochondrial function and increased antioxidant activity, making them more resistant to ischemia-reperfusion injury–acute kidney injury. The study highlights a new role of the multifaceted protein DNA-binding protein-A, which could be potentially therapeutically exploited.
急性肾损伤仍然与高发病率和高死亡率有关。Reichardt 等人研究了 DNA 结合蛋白-A(Ybx3)在缺血再灌注损伤诱发的急性肾损伤中的作用,发现缺乏 Ybx3 的小鼠线粒体功能发生改变,抗氧化活性增强,从而对缺血再灌注损伤-急性肾损伤具有更强的抵抗力。这项研究强调了DNA结合蛋白-A这种多层面蛋白的新作用,它有可能被用于治疗。
{"title":"DNA-binding protein-A: a multitool in tubular epithelial cells","authors":"","doi":"10.1016/j.kint.2024.05.022","DOIUrl":"10.1016/j.kint.2024.05.022","url":null,"abstract":"<div><p>Acute kidney injury is still associated with high morbidity and mortality. Reichardt <em>et al.</em> investigated DNA-binding protein-A (<em>Ybx3</em>) in acute kidney injury induced by ischemia-reperfusion injury and found that mice lacking <em>Ybx3</em> have altered mitochondrial function and increased antioxidant activity, making them more resistant to ischemia-reperfusion injury–acute kidney injury. The study highlights a new role of the multifaceted protein DNA-binding protein-A, which could be potentially therapeutically exploited.</p></div>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":null,"pages":null},"PeriodicalIF":14.8,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141637983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-18DOI: 10.1016/j.kint.2024.05.017
{"title":"Reducing serum phosphate level: how low should we go?","authors":"","doi":"10.1016/j.kint.2024.05.017","DOIUrl":"10.1016/j.kint.2024.05.017","url":null,"abstract":"","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":null,"pages":null},"PeriodicalIF":14.8,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141637987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-14DOI: 10.1016/j.kint.2024.07.002
Benjamin D Humphreys
{"title":"Sox9 flips the switch between regeneration and fibrosis.","authors":"Benjamin D Humphreys","doi":"10.1016/j.kint.2024.07.002","DOIUrl":"10.1016/j.kint.2024.07.002","url":null,"abstract":"","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":null,"pages":null},"PeriodicalIF":14.8,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141620295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-09DOI: 10.1016/j.kint.2024.05.028
ATP depletion plays a central role in the pathogenesis of kidney diseases. Recently, we reported spatiotemporal intracellular ATP dynamics during ischemia reperfusion (IR) using GO-ATeam2 mice systemically expressing an ATP biosensor. However, observation from the kidney surface did not allow visualization of deeper nephrons or accurate evaluation of ATP synthesis pathways. Here, we established a novel ATP imaging system using slice culture of GO-ATeam2 mouse kidneys, evaluated the ATP synthesis pathway, and analyzed intracellular ATP dynamics using an ex vivo IR-mimicking model and a cisplatin nephropathy model. Proximal tubules (PTs) were found to be strongly dependent on oxidative phosphorylation (OXPHOS) using the inhibitor oligomycin A, whereas podocytes relied on both OXPHOS and glycolysis using phloretin an active transport inhibitor of glucose. We also confirmed that an ex vivo IR-mimicking model could recapitulate ATP dynamics in vivo; ATP recovery in PTs after reoxygenation varied depending on anoxic time length, whereas ATP in distal tubules (DTs) recovered well even after long-term anoxia. After cisplatin administration, ATP levels in PTs decreased first, followed by a decrease in DTs. An organic cation transporter 2 inhibitor, cimetidine, suppressed cisplatin uptake in kidney slices, leading to better ATP recovery in PTs, but not in DTs. Finally, we confirmed that a mitochondria protection reagent (Mitochonic Acid 5) delayed the cisplatin-induced ATP decrease in PTs. Thus, our novel system may provide new insights into the energy dynamics and pathogenesis of kidney disease.
ATP 消耗在肾脏疾病的发病机制中起着核心作用。最近,我们利用系统表达 ATP 生物传感器的 GO-ATeam2 小鼠报道了缺血再灌注(IR)期间细胞内 ATP 的时空动态。然而,从肾脏表面进行观察无法观察到更深的肾小球,也无法准确评估 ATP 合成途径。在这里,我们利用 GO-ATeam2 小鼠肾脏切片培养建立了一种新型 ATP 成像系统,评估了 ATP 合成途径,并利用体内外红外模拟模型和顺铂肾病模型分析了细胞内 ATP 动态。使用抑制剂寡霉素 A 发现近端肾小管(PTs)强烈依赖氧化磷酸化(OXPHOS),而使用葡萄糖主动转运抑制剂 phloretin 发现荚膜细胞同时依赖 OXPHOS 和糖酵解。我们还证实,体内外红外模拟模型可以再现体内的 ATP 动态;PT 在复氧后的 ATP 恢复因缺氧时间长短而异,而远端肾小管(DT)中的 ATP 即使在长期缺氧后也能很好地恢复。施用顺铂后,PT 中的 ATP 水平首先下降,随后是 DT 的下降。有机阳离子转运体2抑制剂西咪替丁抑制了肾切片对顺铂的吸收,从而使PT中的ATP恢复得更好,但DT中的ATP却没有恢复。最后,我们证实线粒体保护试剂(线粒体酸 5)可延缓顺铂诱导的 PTs ATP 减少。因此,我们的新系统可以为肾脏疾病的能量动力学和发病机制提供新的见解。
{"title":"Visualization of intracellular ATP dynamics in different nephron segments under pathophysiological conditions using the kidney slice culture system","authors":"","doi":"10.1016/j.kint.2024.05.028","DOIUrl":"10.1016/j.kint.2024.05.028","url":null,"abstract":"<div><p>ATP depletion plays a central role in the pathogenesis of kidney diseases. Recently, we reported spatiotemporal intracellular ATP dynamics during ischemia reperfusion (IR) using GO-ATeam2 mice systemically expressing an ATP biosensor. However, observation from the kidney surface did not allow visualization of deeper nephrons or accurate evaluation of ATP synthesis pathways. Here, we established a novel ATP imaging system using slice culture of GO-ATeam2 mouse kidneys, evaluated the ATP synthesis pathway, and analyzed intracellular ATP dynamics using an <em>ex vivo</em> IR-mimicking model and a cisplatin nephropathy model. Proximal tubules (PTs) were found to be strongly dependent on oxidative phosphorylation (OXPHOS) using the inhibitor oligomycin A, whereas podocytes relied on both OXPHOS and glycolysis using phloretin an active transport inhibitor of glucose. We also confirmed that an <em>ex vivo</em> IR-mimicking model could recapitulate ATP dynamics <em>in vivo</em>; ATP recovery in PTs after reoxygenation varied depending on anoxic time length, whereas ATP in distal tubules (DTs) recovered well even after long-term anoxia. After cisplatin administration, ATP levels in PTs decreased first, followed by a decrease in DTs. An organic cation transporter 2 inhibitor, cimetidine, suppressed cisplatin uptake in kidney slices, leading to better ATP recovery in PTs, but not in DTs. Finally, we confirmed that a mitochondria protection reagent (Mitochonic Acid 5) delayed the cisplatin-induced ATP decrease in PTs. Thus, our novel system may provide new insights into the energy dynamics and pathogenesis of kidney disease.</p></div>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":null,"pages":null},"PeriodicalIF":14.8,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0085253824004095/pdfft?md5=5159a63c60d6104f093f829b2a59abc5&pid=1-s2.0-S0085253824004095-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141600315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-06DOI: 10.1016/j.kint.2024.05.032
Guillaume Dorval, Manuela Colucci, Olivia Boyer
{"title":"B-cell repertoire and functions in idiopathic nephrotic syndrome: what to learn from single-cell RNA sequencing?","authors":"Guillaume Dorval, Manuela Colucci, Olivia Boyer","doi":"10.1016/j.kint.2024.05.032","DOIUrl":"10.1016/j.kint.2024.05.032","url":null,"abstract":"","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":null,"pages":null},"PeriodicalIF":14.8,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141559049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-04DOI: 10.1016/j.kint.2024.06.007
Hiddo J L Heerspink, Dustin J Little, Lars Frison, Samvel B Gasparyan, Christoph Wanner, Niels Jongs, Douwe Postmus
Glomerular filtration rate (GFR) decline is used as surrogate endpoint for kidney failure. Interventions that reduce chronic kidney disease (CKD) progression often exert acute GFR reductions which differ from their long-term benefits and complicate the estimation of long-term benefit. Here, we assessed the utility of two alternative trial designs (wash-out design and active run-in randomized withdrawal design) that attempt to exclude the impact of acute effects. Post-hoc analyses of two clinical trials that characterized the effect of an intervention with acute reductions in GFR were conducted. The two trials included a wash-out period (EMPA-REG Outcome testing empagliflozin vs placebo) or an active run-in period with a randomized withdrawal (SONAR testing atrasentan vs placebo). We compared the drug effect on GFR decline calculated from the first on-treatment visit to the end of treatment (chronic slope in a standard randomized trial design) with GFR change calculated from randomization to end of wash out, or GFR change from treatment-specific baseline GFR values (GFR at start-of-run-in for placebo and end-of-run-in for atrasentan) until end-of-treatment. The effect of empagliflozin versus placebo on chronic GFR slope was 1.72 (95% confidence interval 1.49-1.94) mL/min/1.73 m2/year, similar to total GFR decline from baseline to the end of wash-out period using a linear mixed model 1.64 (1.44-1.85) mL/min/1.73 m2/year). The effect of atrasentan versus placebo on chronic GFR slope was 0.72 (0.32-1.11) mL/min/1.73 m2/year, similar to total slope from a single slope model when estimated from treatment specific baseline GFR values 0.77 (0.39-1.14) mL/min/1.73 m2/year). Statistical power of the two designs outperformed the standard randomized design. Thus, wash-out and active-run-in randomized-withdrawal trial designs are appropriate models to compute treatment effects on GFR decline.
肾小球滤过率(GFR)下降被用作肾衰竭的替代终点。减少慢性肾脏病(CKD)进展的干预措施通常会使肾小球滤过率急性下降,这与其长期益处不同,也使长期益处的评估变得复杂。在此,我们评估了试图排除急性效应影响的两种替代试验设计(冲出设计和积极跑步随机撤出设计)的实用性。我们对两项临床试验的效果进行了事后分析,这两项试验的特点是干预措施会导致 GFR 急性下降。这两项试验包括一个冲出期(EMPAREG-Outcome 试验:安帕格列嗪与安慰剂对比)或一个随机停药的积极运行期(SONAR 试验:阿曲生坦与安慰剂对比)。我们比较了从首次接受治疗到治疗结束(标准随机试验设计中的慢性效应)所计算的药物对GFR下降的影响,以及从随机化到退出治疗结束所计算的GFR变化,或从治疗特定基线GFR值(安慰剂为运行开始时的GFR,阿曲生坦为运行结束时的GFR)到治疗结束的GFR变化。与安慰剂相比,empagliflozin对慢性GFR斜率的影响为1.72(95%置信区间为1.49-1.94)毫升/分钟/1.73平方米/年,与使用线性混合模型计算的从基线到冲洗期结束的GFR总下降率1.64(1.44-1.85)毫升/分钟/1.73平方米/年相似。)阿曲生坦与安慰剂相比对慢性 GFR 斜率的影响为 0.72 (0.32-1.11) mL/min/1.73m2 /年,与根据治疗特定基线 GFR 值估算的单一斜率模型总斜率 0.77 (0.39-1.14) mL/min/1.73m2 /年相似。)两种设计的统计功率优于标准随机设计。因此,"冲出 "和 "主动-运行-输入 "随机-退出试验设计是计算治疗对 GFR 下降影响的合适模型。
{"title":"Clinical trial designs to assess treatment effects on glomerular filtration rate decline.","authors":"Hiddo J L Heerspink, Dustin J Little, Lars Frison, Samvel B Gasparyan, Christoph Wanner, Niels Jongs, Douwe Postmus","doi":"10.1016/j.kint.2024.06.007","DOIUrl":"10.1016/j.kint.2024.06.007","url":null,"abstract":"<p><p>Glomerular filtration rate (GFR) decline is used as surrogate endpoint for kidney failure. Interventions that reduce chronic kidney disease (CKD) progression often exert acute GFR reductions which differ from their long-term benefits and complicate the estimation of long-term benefit. Here, we assessed the utility of two alternative trial designs (wash-out design and active run-in randomized withdrawal design) that attempt to exclude the impact of acute effects. Post-hoc analyses of two clinical trials that characterized the effect of an intervention with acute reductions in GFR were conducted. The two trials included a wash-out period (EMPA-REG Outcome testing empagliflozin vs placebo) or an active run-in period with a randomized withdrawal (SONAR testing atrasentan vs placebo). We compared the drug effect on GFR decline calculated from the first on-treatment visit to the end of treatment (chronic slope in a standard randomized trial design) with GFR change calculated from randomization to end of wash out, or GFR change from treatment-specific baseline GFR values (GFR at start-of-run-in for placebo and end-of-run-in for atrasentan) until end-of-treatment. The effect of empagliflozin versus placebo on chronic GFR slope was 1.72 (95% confidence interval 1.49-1.94) mL/min/1.73 m<sup>2</sup>/year, similar to total GFR decline from baseline to the end of wash-out period using a linear mixed model 1.64 (1.44-1.85) mL/min/1.73 m<sup>2</sup>/year). The effect of atrasentan versus placebo on chronic GFR slope was 0.72 (0.32-1.11) mL/min/1.73 m<sup>2</sup>/year, similar to total slope from a single slope model when estimated from treatment specific baseline GFR values 0.77 (0.39-1.14) mL/min/1.73 m<sup>2</sup>/year). Statistical power of the two designs outperformed the standard randomized design. Thus, wash-out and active-run-in randomized-withdrawal trial designs are appropriate models to compute treatment effects on GFR decline.</p>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":null,"pages":null},"PeriodicalIF":14.8,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141538005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-02DOI: 10.1016/j.kint.2024.06.012
Richard B Dorshow, Martin P Debreczeny, Stuart L Goldstein, Jeng-Jong Shieh
The fluorescent compound relmapirazin has been rationally designed for use in point-of-care measurement of glomerular filtration rate (GFR), with attributes including negligible protein binding, negligible metabolites in vivo, negligible tubular secretion, and excellent chemical and photo stability. Twenty-four nonclinical assays were performed in accordance with FDA requirements yielding negligible toxicology concerns. Here, a clinical study was performed to validate relmapirazin as a GFR tracer in patients by comparison to iohexol. This was evaluated in 120 adults at three clinical sites with eGFR values ranging from normal to Stage 4 chronic kidney disease. Relmapirazin and iohexol were administered intravenously in consecutive boluses to each subject and serial blood samples obtained over the subsequent 12 hours. Plasma concentrations were measured and the corresponding plasma GFR for each agent was determined using a standard two-compartment pharmacokinetic assessment. Urine from each subject was collected for the entire 12-hour study period to measure the amount of administered dose appearing in the urine. A near perfect linear regression correlation was observed between the GFRs measured by these two tracers (r2=0.99). Bland-Altman analysis confirmed agreement between these two measures of GFR (limits of agreement -7.0 to +5.6 mL/min; mean of -0.7 mL/min). The GFR determined by relmapirazin was independent of GFR stratification by chronic kidney disease stage, and importantly by race. The percent of the administered relmapirazin dose recovered in the urine was greater than or equal to that of iohexol with no reported severe adverse events. Thus, relmapirazin may be used as a GFR tracer agent in humans.
荧光化合物 relmapirazin 经过合理设计,可用于肾小球滤过率(GFR)的床旁测量,其特性包括可忽略的蛋白结合、可忽略的体内代谢物、可忽略的肾小管分泌以及出色的化学和光稳定性。根据 FDA 的要求进行了 24 项非临床试验,结果显示毒理学方面的问题可以忽略不计。在此,我们进行了一项临床研究,通过与碘海醇的比较,验证了雷马吡嗪作为患者肾小球滤过率示踪剂的有效性。这项研究在三个临床地点对 120 名成人进行了评估,这些成人的 eGFR 值从正常到 4 期慢性肾病不等。对每位受试者连续静脉注射瑞马吡嗪和碘海醇,并在随后的 12 小时内连续采集血样。采用标准的两室药代动力学评估法测定每种药物的血浆浓度和相应的血浆 GFR。在整个 12 小时的研究期间,收集每个受试者的尿液,以测定尿液中出现的给药剂量。通过这两种示踪剂测得的 GFR 之间存在近乎完美的线性回归相关性(r2=0.99)。Bland-Altman 分析证实了这两种 GFR 测量方法之间的一致性(一致性范围为 -7.0 至 +5.6 毫升/分钟;平均值为 -0.7 毫升/分钟)。雷马比拉嗪确定的 GFR 与按慢性肾病分期进行的 GFR 分层无关,重要的是与种族无关。从尿液中回收的雷马拉嗪剂量百分比大于或等于碘海醇,且无严重不良反应报告。因此,雷马哌嗪可用作人体肾小球滤过率示踪剂。
{"title":"Clinical validation of the novel fluorescent glomerular filtration rate tracer agent relmapirazin (MB-102).","authors":"Richard B Dorshow, Martin P Debreczeny, Stuart L Goldstein, Jeng-Jong Shieh","doi":"10.1016/j.kint.2024.06.012","DOIUrl":"10.1016/j.kint.2024.06.012","url":null,"abstract":"<p><p>The fluorescent compound relmapirazin has been rationally designed for use in point-of-care measurement of glomerular filtration rate (GFR), with attributes including negligible protein binding, negligible metabolites in vivo, negligible tubular secretion, and excellent chemical and photo stability. Twenty-four nonclinical assays were performed in accordance with FDA requirements yielding negligible toxicology concerns. Here, a clinical study was performed to validate relmapirazin as a GFR tracer in patients by comparison to iohexol. This was evaluated in 120 adults at three clinical sites with eGFR values ranging from normal to Stage 4 chronic kidney disease. Relmapirazin and iohexol were administered intravenously in consecutive boluses to each subject and serial blood samples obtained over the subsequent 12 hours. Plasma concentrations were measured and the corresponding plasma GFR for each agent was determined using a standard two-compartment pharmacokinetic assessment. Urine from each subject was collected for the entire 12-hour study period to measure the amount of administered dose appearing in the urine. A near perfect linear regression correlation was observed between the GFRs measured by these two tracers (r<sup>2</sup>=0.99). Bland-Altman analysis confirmed agreement between these two measures of GFR (limits of agreement -7.0 to +5.6 mL/min; mean of -0.7 mL/min). The GFR determined by relmapirazin was independent of GFR stratification by chronic kidney disease stage, and importantly by race. The percent of the administered relmapirazin dose recovered in the urine was greater than or equal to that of iohexol with no reported severe adverse events. Thus, relmapirazin may be used as a GFR tracer agent in humans.</p>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":null,"pages":null},"PeriodicalIF":14.8,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01DOI: 10.1016/j.kint.2024.05.031
Germaine Wong, Chandana Guha, Kylie-Ann Mallitt, Anita van Zwieten, Rabia Khalid, Anna Francis, Allison Jaure, Siah Kim, Armando Teixeira-Pinto, Martha Aquino, Amelie Bernier-Jean, David W Johnson, Deirdre Hahn, Donna Reidlinger, Elizabeth G Ryan, Fiona Mackie, Hugh McCarthy, Julie Varghese, Charani Kiriwandeniya, Kirsten Howard, Nicholas Larkins, Luke Macauley, Amanda Walker, Martin Howell, Patrina Caldwell, Reginald Woodleigh, Shilpa Jesudason, Simon Carter, Sean Kennedy, Stephen Alexander, Steve McTaggart, Jonathan C Craig, Carmel M Hawley
Patient navigators enable adult patients to circumnavigate complex health systems, improving access to health care and outcomes. Here, we aimed to evaluate the effects of a patient navigation program in children with chronic kidney disease (CKD). In this multi-center, randomized controlled trial, we randomly assigned children (aged 0-16 years) with CKD stages 1-5 (including children on dialysis or with kidney transplants), from low socioeconomic status backgrounds, and/or residing in remote areas, to receive patient navigation at randomization (immediate) or at six months (waitlist). The primary outcome was self-rated health (SRH) of participating children at six months, using intention to treat analysis. Secondary outcomes included caregivers' SRH and satisfaction with health care, children's quality of life, hospitalizations, and missed school days. Repeated measures of the primary outcome from baseline to six months were analyzed using cumulative logit mixed effects models. Semi-structured interviews were thematically evaluated. Of 398 screened children, 162 were randomized (80 immediate and 82 waitlist); mean age (standard deviation) of 8.8 (4.8) years with 64.8% male. SRH was not significantly different between the immediate and wait-listed groups at six months. There were also no differences across all secondary outcomes between the two groups. Caregivers' perspectives were reflected in seven themes: easing mental strain, facilitating care coordination, strengthening capacity to provide care, reinforcing care collaborations, alleviating family tensions, inability to build rapport and unnecessary support. Thus, in children with CKD, self-rated health may not improve in response to a navigator program, but caregivers gained skills related to providing and accessing care.
{"title":"The randomized controlled trial (NAVKIDS<sup>2</sup>) of a patient navigator program created for children with chronic kidney disease.","authors":"Germaine Wong, Chandana Guha, Kylie-Ann Mallitt, Anita van Zwieten, Rabia Khalid, Anna Francis, Allison Jaure, Siah Kim, Armando Teixeira-Pinto, Martha Aquino, Amelie Bernier-Jean, David W Johnson, Deirdre Hahn, Donna Reidlinger, Elizabeth G Ryan, Fiona Mackie, Hugh McCarthy, Julie Varghese, Charani Kiriwandeniya, Kirsten Howard, Nicholas Larkins, Luke Macauley, Amanda Walker, Martin Howell, Patrina Caldwell, Reginald Woodleigh, Shilpa Jesudason, Simon Carter, Sean Kennedy, Stephen Alexander, Steve McTaggart, Jonathan C Craig, Carmel M Hawley","doi":"10.1016/j.kint.2024.05.031","DOIUrl":"10.1016/j.kint.2024.05.031","url":null,"abstract":"<p><p>Patient navigators enable adult patients to circumnavigate complex health systems, improving access to health care and outcomes. Here, we aimed to evaluate the effects of a patient navigation program in children with chronic kidney disease (CKD). In this multi-center, randomized controlled trial, we randomly assigned children (aged 0-16 years) with CKD stages 1-5 (including children on dialysis or with kidney transplants), from low socioeconomic status backgrounds, and/or residing in remote areas, to receive patient navigation at randomization (immediate) or at six months (waitlist). The primary outcome was self-rated health (SRH) of participating children at six months, using intention to treat analysis. Secondary outcomes included caregivers' SRH and satisfaction with health care, children's quality of life, hospitalizations, and missed school days. Repeated measures of the primary outcome from baseline to six months were analyzed using cumulative logit mixed effects models. Semi-structured interviews were thematically evaluated. Of 398 screened children, 162 were randomized (80 immediate and 82 waitlist); mean age (standard deviation) of 8.8 (4.8) years with 64.8% male. SRH was not significantly different between the immediate and wait-listed groups at six months. There were also no differences across all secondary outcomes between the two groups. Caregivers' perspectives were reflected in seven themes: easing mental strain, facilitating care coordination, strengthening capacity to provide care, reinforcing care collaborations, alleviating family tensions, inability to build rapport and unnecessary support. Thus, in children with CKD, self-rated health may not improve in response to a navigator program, but caregivers gained skills related to providing and accessing care.</p>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":null,"pages":null},"PeriodicalIF":14.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-28DOI: 10.1016/j.kint.2024.05.030
Baseline kidney function following kidney transplantation is often used in research and clinical decision-making yet is not well defined. Here, a method to determine baseline function was proposed and validated on three single-center retrospective cohorts consisting of 922 patients from Belgium (main cohort) and two validation cohorts of 987 patients from the Netherlands and 519 patients from Germany. For each transplant, a segmented regression model was fitted on the estimated glomerular filtration rate (eGFR) evolution during the first-year post-transplantation. This yielded estimates for change point timing, rate of eGFR change before and after change point and eGFR value at change point, now considered the “baseline function”. Associations of eGFR evolution with recipient/donor characteristics and the graft failure rate were assessed with linear regression and Cox regression respectively. The change point occurred on average at an eGFR value of 43.7±14.6 mL/min/1.73m2, at a median time of 6.5 days post-transplantation. Despite significant associations with several baseline donor-recipient characteristics (particularly, donor type; living vs deceased), the predictive value of these characteristics for eGFR value and timing of the change point was limited. This followed from a large heterogeneity within eGFR trajectories, which in turn indicated that favorable levels of kidney function could be reached despite a suboptimal initial evolution. Segmented regression consistently provided a good fit to early eGFR evolution, and its estimate of the change point can be a useful reference value in future analyses. Thus, our study shows that baseline kidney function after transplantation is heterogeneous and partly related to pretransplant donor characteristics.
{"title":"An observational cohort study examined the change point of kidney function stabilization in the initial period after transplantation","authors":"","doi":"10.1016/j.kint.2024.05.030","DOIUrl":"10.1016/j.kint.2024.05.030","url":null,"abstract":"<div><p>Baseline kidney function following kidney transplantation is often used in research and clinical decision-making yet is not well defined. Here, a method to determine baseline function was proposed and validated on three single-center retrospective cohorts consisting of 922 patients from Belgium (main cohort) and two validation cohorts of 987 patients from the Netherlands and 519 patients from Germany. For each transplant, a segmented regression model was fitted on the estimated glomerular filtration rate (eGFR) evolution during the first-year post-transplantation. This yielded estimates for change point timing, rate of eGFR change before and after change point and eGFR value at change point, now considered the “baseline function”. Associations of eGFR evolution with recipient/donor characteristics and the graft failure rate were assessed with linear regression and Cox regression respectively. The change point occurred on average at an eGFR value of 43.7±14.6 mL/min/1.73m<sup>2</sup>, at a median time of 6.5 days post-transplantation. Despite significant associations with several baseline donor-recipient characteristics (particularly, donor type; living vs deceased), the predictive value of these characteristics for eGFR value and timing of the change point was limited. This followed from a large heterogeneity within eGFR trajectories, which in turn indicated that favorable levels of kidney function could be reached despite a suboptimal initial evolution. Segmented regression consistently provided a good fit to early eGFR evolution, and its estimate of the change point can be a useful reference value in future analyses. Thus, our study shows that baseline kidney function after transplantation is heterogeneous and partly related to pretransplant donor characteristics.</p></div>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":null,"pages":null},"PeriodicalIF":14.8,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0085253824004484/pdfft?md5=e360cfc3f8026564e835ef8138a2017e&pid=1-s2.0-S0085253824004484-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}