Pub Date : 2024-01-01Epub Date: 2023-12-13DOI: 10.1159/000535754
Juan A Medaura, Meijiao Zhou, Linda H Ficociello, Michael S Anger, Stuart M Sprague
Introduction: Sucroferric oxyhydroxide (SO), a non-calcium, chewable, iron-based phosphate binder (PB), effectively lowers serum phosphorus (sP) concentrations while reducing pill burden relative to other PBs. To date, SO studies have largely examined treatment-experienced, prevalent hemodialysis populations. We aimed to explore the role of first-line SO initiated during the first year of dialysis.
Methods: We retrospectively analyzed deidentified data from adults receiving in-center hemodialysis who were prescribed SO monotherapy within the first year of hemodialysis as part of routine clinical care. All patients continuing SO monotherapy for 12 months were included. Changes from baseline in sP, achievement of sP ≤5.5 and ≤4.5 mg/dL, and other laboratory parameters were analyzed quarterly for 1 year.
Results: The overall cohort included 596 patients, 286 of whom had a dialysis vintage ≤3 months. In the 3 months preceding SO initiation, sP rapidly increased (mean increases of 1.02 and 1.65 mg/dL in the overall cohort and incident cohort, respectively). SO treatment was associated with significant decreases in quarterly sP (mean decreases of 0.26-0.36; p < 0.0001 for each quarter and overall). While receiving SO, 55-60% of patients achieved sP ≤5.5 mg/dL and 21-24% achieved sP ≤4.5 mg/dL (p < 0.0001 for each quarter and overall vs. baseline). Daily PB pill burden was approximately 4 pills. Serum calcium concentrations increased and intact parathyroid hormone concentrations decreased during SO treatment (p < 0.0001 vs. baseline).
Conclusions: Among patients on hemodialysis, initiating SO as a first-line PB resulted in significant reductions in sP while maintaining a relatively low PB pill burden.
{"title":"Serum Phosphorus Management with Sucroferric Oxyhydroxide as a First-Line Phosphate Binder within the First Year of Hemodialysis.","authors":"Juan A Medaura, Meijiao Zhou, Linda H Ficociello, Michael S Anger, Stuart M Sprague","doi":"10.1159/000535754","DOIUrl":"10.1159/000535754","url":null,"abstract":"<p><strong>Introduction: </strong>Sucroferric oxyhydroxide (SO), a non-calcium, chewable, iron-based phosphate binder (PB), effectively lowers serum phosphorus (sP) concentrations while reducing pill burden relative to other PBs. To date, SO studies have largely examined treatment-experienced, prevalent hemodialysis populations. We aimed to explore the role of first-line SO initiated during the first year of dialysis.</p><p><strong>Methods: </strong>We retrospectively analyzed deidentified data from adults receiving in-center hemodialysis who were prescribed SO monotherapy within the first year of hemodialysis as part of routine clinical care. All patients continuing SO monotherapy for 12 months were included. Changes from baseline in sP, achievement of sP ≤5.5 and ≤4.5 mg/dL, and other laboratory parameters were analyzed quarterly for 1 year.</p><p><strong>Results: </strong>The overall cohort included 596 patients, 286 of whom had a dialysis vintage ≤3 months. In the 3 months preceding SO initiation, sP rapidly increased (mean increases of 1.02 and 1.65 mg/dL in the overall cohort and incident cohort, respectively). SO treatment was associated with significant decreases in quarterly sP (mean decreases of 0.26-0.36; p < 0.0001 for each quarter and overall). While receiving SO, 55-60% of patients achieved sP ≤5.5 mg/dL and 21-24% achieved sP ≤4.5 mg/dL (p < 0.0001 for each quarter and overall vs. baseline). Daily PB pill burden was approximately 4 pills. Serum calcium concentrations increased and intact parathyroid hormone concentrations decreased during SO treatment (p < 0.0001 vs. baseline).</p><p><strong>Conclusions: </strong>Among patients on hemodialysis, initiating SO as a first-line PB resulted in significant reductions in sP while maintaining a relatively low PB pill burden.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10994597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138795936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2023-08-14DOI: 10.1159/000533600
Caroline W H de Fijter, Joanna Stachowska-Pietka, Jacek Waniewski, Bengt Lindholm
Recently, hyperosmolar hyponatremia following excessive off-label use of two exchanges of 2 L icodextrin daily during peritoneal dialysis (PD) was reported. We encountered a cluster of 3 cases of PD patients who developed hyperosmolar hyponatremia during on-label use of icodextrin. This appeared to be due to absorption of icodextrin since after stopping icodextrin, the serum sodium level and osmol gap returned to normal, while a rechallenge again resulted in hyperosmolar hyponatremia. We excluded higher than usual concentrations of specific fractions of dextrins in fresh icodextrin dialysis fluid (lot numbers of used batches were checked by manufacturer). We speculate that in our patients, either an exaggerated degradation of polysaccharide chains by α-amylase activity in dialysate, lymph, and interstitium and/or rapid hydrolysis of the absorbed larger degradation products in the circulation may have contributed to the hyperosmolality observed, with the concentration of oligosaccharides exceeding the capacity of intracellular enzymes (in particular maltase) to metabolize these products to glucose. Both hyponatremia and hyperosmolality are risk factors for poor outcomes in PD patients. Less conventional PD prescriptions such as off-label use of two exchanges of 2 L icodextrin might raise the risk of this threatening side effect. This brief report is intended to create awareness of a rare complication of on-label icodextrin use in a subset of PD patients and/or PD prescriptions.
最近有报道称,在腹膜透析(PD)过程中,腹膜透析患者在标示外过量使用每天两次的 2 升冰糖糊精后出现了高渗性低钠血症。我们发现有 3 例腹膜透析患者在标示内使用伊可新时出现了高渗性低钠血症。这似乎是由于吸收了冰可糊精所致,因为在停止使用冰可糊精后,血清钠水平和渗透压缺口恢复正常,而再次使用时又会出现高渗透压性低钠血症。我们排除了新鲜冰糊精透析液中特定馏分糊精浓度高于正常值的可能性(所用批次的批号由制造商核对)。我们推测,在我们的患者中,透析液、淋巴和间质中的α-淀粉酶活性对多糖链的过度降解和/或吸收的较大降解产物在循环中的快速水解可能是导致高渗的原因,因为低聚糖的浓度超过了细胞内酶(尤其是麦芽糖酶)将这些产物代谢为葡萄糖的能力。低钠血症和高渗透压都是导致帕金森病患者预后不良的危险因素。不那么常规的帕金森病处方,如标签外使用两次交换的 2 L 冰糖糊精,可能会增加出现这种威胁性副作用的风险。这份简短的报告旨在让人们认识到,在标示内使用冰解糊精会在部分帕金森病患者和/或帕金森病处方中引起一种罕见的并发症。
{"title":"High Osmol Gap Hyponatremia Caused by Icodextrin: A Case Series Report.","authors":"Caroline W H de Fijter, Joanna Stachowska-Pietka, Jacek Waniewski, Bengt Lindholm","doi":"10.1159/000533600","DOIUrl":"10.1159/000533600","url":null,"abstract":"<p><p>Recently, hyperosmolar hyponatremia following excessive off-label use of two exchanges of 2 L icodextrin daily during peritoneal dialysis (PD) was reported. We encountered a cluster of 3 cases of PD patients who developed hyperosmolar hyponatremia during on-label use of icodextrin. This appeared to be due to absorption of icodextrin since after stopping icodextrin, the serum sodium level and osmol gap returned to normal, while a rechallenge again resulted in hyperosmolar hyponatremia. We excluded higher than usual concentrations of specific fractions of dextrins in fresh icodextrin dialysis fluid (lot numbers of used batches were checked by manufacturer). We speculate that in our patients, either an exaggerated degradation of polysaccharide chains by α-amylase activity in dialysate, lymph, and interstitium and/or rapid hydrolysis of the absorbed larger degradation products in the circulation may have contributed to the hyperosmolality observed, with the concentration of oligosaccharides exceeding the capacity of intracellular enzymes (in particular maltase) to metabolize these products to glucose. Both hyponatremia and hyperosmolality are risk factors for poor outcomes in PD patients. Less conventional PD prescriptions such as off-label use of two exchanges of 2 L icodextrin might raise the risk of this threatening side effect. This brief report is intended to create awareness of a rare complication of on-label icodextrin use in a subset of PD patients and/or PD prescriptions.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10372848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2023-11-06DOI: 10.1159/000534829
Firas F Alkaff, Daan Kremer, Charlotte A Te Velde-Keyzer, Jacob van den Born, Stefan P Berger, Gozewijn D Laverman, Lee-Ming Chuang, Tzu-Ling Tseng, Stephan J L Bakker
Introduction: Urinary fetuin-A has been identified as a biomarker for acute kidney injury and is proposed as a biomarker for early detection of kidney function decline. We investigated whether fetuin-A could serve as a marker of graft failure in kidney transplant recipients (KTRs).
Methods: Data of KTR with a functioning graft ≥1 year that were enrolled in the TransplantLines Food and Nutrition Biobank and cohort study were used. Graft failure was defined as the need for re-transplantation or (re-)initiation of dialysis. Urinary fetuin-A was measured using an enzyme-linked immunosorbent assay kit that detected post-translationally modified fetuin-A in the urine (uPTM-FetA). In the main analyses, 24h uPTM-FetA excretion was used. In the sensitivity analyses, we excluded the outliers in 24h uPTM-FetA excretion, and we used uPTM-FetA concentration and uPTM-FetA concentration indexed for creatinine instead of 24h uPTM-FetA excretion.
Results: A total of 627 KTRs (age 53 ± 13 years, 42% females) were included at 5.3 (1.9-12.2) years after transplantation. The estimated glomerular filtration rate (eGFR) was 52 ± 20 mL/min/1.73 m2 and uPTM-FetA excretion was 34 (17-74) µg/24 h. During a median follow-up of 5.3 (4.5-6.0) years after baseline measurements, 73 (12%) KTRs developed graft failure. The association of 24h uPTM-FetA excretion with increased risk of graft failure was not constant over time, with increased risk only observed after 3 years from baseline measurements, independent of potential confounders including kidney function and 24 h urinary protein excretion (hazard ratio per doubling of 24h uPTM-FetA excretion = 1.31; 95% confidence interval = 1.06-1.61). This finding was robust in the sensitivity analyses.
Conclusions: Our findings suggest that uPTM-FetA can be used as a marker for early detection of graft failure in KTR. Further studies are needed to confirm our findings.
引言:尿胎蛋白-A已被确定为急性肾损伤的生物标志物,并被提议作为早期检测肾功能下降的生物标志。我们研究了胎球蛋白-A是否可以作为肾移植受者(KTR)移植物衰竭的标志物。方法:使用TransplantLines Food and Nutrition Biobank和Cohort研究中登记的移植物功能≥1年的KTR数据。移植物衰竭被定义为需要再次移植或(重新)开始透析)。使用检测尿液中翻译后修饰的胎蛋白-A的酶联免疫吸附测定试剂盒(uPTM-FetA)测量尿中胎蛋白-A。在主要分析中,使用24小时uPTM-FetA排泄。在敏感性分析中,我们排除了24小时uPTM-FetA排泄的异常值,并使用uPTM-FetA浓度和uPTM-Fita浓度作为肌酐指数,而不是24小时uPTM-FetA排出。结果:共有627 KTR(年龄53±13岁,42%为女性)在移植后5.3[1.9-12.2]年被纳入。估计肾小球滤过率(eGFR)为52±20 mL/min/1.73 m2,uPTM-FetA排泄量为34[17-74]µg/24h。在基线测量后5.3[4.5-6.0]年的中位随访期间,73(12%)KTR出现移植物衰竭。24小时uPTM-FetA排泄与移植物衰竭风险增加的相关性并非随时间而恒定,仅在基线测量后3年后观察到风险增加,独立于潜在的混杂因素,包括肾功能和24小时尿蛋白排泄量(24小时uPTM-FetA排泄量每增加一倍的风险比=1.31;95%置信区间=1.06-1.61)。这一发现在敏感性分析中是稳健的。结论:我们的研究结果表明uPTM-FetA可以作为KTR移植物衰竭早期检测的标志物。需要进一步的研究来证实我们的发现。
{"title":"Urinary Post-Translationally Modified Fetuin-A Protein Is Associated with Increased Risk of Graft Failure in Kidney Transplant Recipients.","authors":"Firas F Alkaff, Daan Kremer, Charlotte A Te Velde-Keyzer, Jacob van den Born, Stefan P Berger, Gozewijn D Laverman, Lee-Ming Chuang, Tzu-Ling Tseng, Stephan J L Bakker","doi":"10.1159/000534829","DOIUrl":"10.1159/000534829","url":null,"abstract":"<p><strong>Introduction: </strong>Urinary fetuin-A has been identified as a biomarker for acute kidney injury and is proposed as a biomarker for early detection of kidney function decline. We investigated whether fetuin-A could serve as a marker of graft failure in kidney transplant recipients (KTRs).</p><p><strong>Methods: </strong>Data of KTR with a functioning graft ≥1 year that were enrolled in the TransplantLines Food and Nutrition Biobank and cohort study were used. Graft failure was defined as the need for re-transplantation or (re-)initiation of dialysis. Urinary fetuin-A was measured using an enzyme-linked immunosorbent assay kit that detected post-translationally modified fetuin-A in the urine (uPTM-FetA). In the main analyses, 24h uPTM-FetA excretion was used. In the sensitivity analyses, we excluded the outliers in 24h uPTM-FetA excretion, and we used uPTM-FetA concentration and uPTM-FetA concentration indexed for creatinine instead of 24h uPTM-FetA excretion.</p><p><strong>Results: </strong>A total of 627 KTRs (age 53 ± 13 years, 42% females) were included at 5.3 (1.9-12.2) years after transplantation. The estimated glomerular filtration rate (eGFR) was 52 ± 20 mL/min/1.73 m2 and uPTM-FetA excretion was 34 (17-74) µg/24 h. During a median follow-up of 5.3 (4.5-6.0) years after baseline measurements, 73 (12%) KTRs developed graft failure. The association of 24h uPTM-FetA excretion with increased risk of graft failure was not constant over time, with increased risk only observed after 3 years from baseline measurements, independent of potential confounders including kidney function and 24 h urinary protein excretion (hazard ratio per doubling of 24h uPTM-FetA excretion = 1.31; 95% confidence interval = 1.06-1.61). This finding was robust in the sensitivity analyses.</p><p><strong>Conclusions: </strong>Our findings suggest that uPTM-FetA can be used as a marker for early detection of graft failure in KTR. Further studies are needed to confirm our findings.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71477110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2024-01-10DOI: 10.1159/000535752
Aurora Pérez-Gómez, Lucie Fernandez, Joost P Schanstra, Julie Klein
{"title":"Klotho and Mortality in Chronic Kidney Disease: Actor, Risk Factor, or Predictor?","authors":"Aurora Pérez-Gómez, Lucie Fernandez, Joost P Schanstra, Julie Klein","doi":"10.1159/000535752","DOIUrl":"10.1159/000535752","url":null,"abstract":"","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11151967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139416085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Sarcopenia and vitamin D deficiency are highly prevalent among patients undergoing haemodialysis. Although vitamin D deficiency, assessed using serum 25-hydroxyvitamin D (25(OH)D) levels, is known to be associated with sarcopenia in the general population, whether serum 25(OH)D levels are associated with sarcopenia in patients undergoing haemodialysis with suppressed renal activation of 25(OH)D remains unclear. This study aimed to examine the association between serum 25(OH)D levels and sarcopenia in patients undergoing haemodialysis.
Methods: Serum 25(OH)D level measurements and assessment of sarcopenia using the Asian Working Group for Sarcopenia criteria were conducted in 95 stable outpatients undergoing maintenance haemodialysis therapy.
Results: Sarcopenia was observed in 22 (23.1%) patients. In multiple logistic regression analysis, serum 25(OH)D levels were associated with sarcopenia (odds ratio [OR] 0.87, 95% confidence interval [CI] 0.77-0.99, p = 0.039) independent of traditional risk factors for sarcopenia. In multiple linear regression analyses, serum 25(OH)D levels were associated with parameters of skeletal muscle mass and strength (β = 0.145, p = 0.046, and β = 0.194, p = 0.020, respectively). The adjusted OR for sarcopenia was 5.60 (95% CI 1.52-20.57, p = 0.009) in the vitamin D deficiency group categorized based on the cut-off serum 25(OH)D level of 10 ng/mL. Regarding model discrimination, adding vitamin D deficiency to the traditional risk factors significantly improved the integrated discrimination improvement score (0.093, p = 0.007).
Conclusion: Lower serum 25(OH)D levels were associated with sarcopenia independent of traditional risk factors in patients undergoing haemodialysis with suppressed vitamin D activation in the kidney. This finding implies that circulating 25(OH)D may have an important relationship with the skeletal muscle function of patients undergoing haemodialysis, and its measurement may be recommended to identify patients at high risk for sarcopenia among those undergoing haemodialysis.
{"title":"Association between Serum 25-Hydroxyvitamin D Levels and Sarcopenia in Patients Undergoing Chronic Haemodialysis.","authors":"Mayuko Hori, Hiroshi Takahashi, Chika Kondo, Fumihito Hayashi, Shigehiro Tokoroyama, Yoshiko Mori, Makoto Tsujita, Yuichi Shirasawa, Asami Takeda, Kunio Morozumi, Shoichi Maruyama","doi":"10.1159/000536582","DOIUrl":"10.1159/000536582","url":null,"abstract":"<p><strong>Introduction: </strong>Sarcopenia and vitamin D deficiency are highly prevalent among patients undergoing haemodialysis. Although vitamin D deficiency, assessed using serum 25-hydroxyvitamin D (25(OH)D) levels, is known to be associated with sarcopenia in the general population, whether serum 25(OH)D levels are associated with sarcopenia in patients undergoing haemodialysis with suppressed renal activation of 25(OH)D remains unclear. This study aimed to examine the association between serum 25(OH)D levels and sarcopenia in patients undergoing haemodialysis.</p><p><strong>Methods: </strong>Serum 25(OH)D level measurements and assessment of sarcopenia using the Asian Working Group for Sarcopenia criteria were conducted in 95 stable outpatients undergoing maintenance haemodialysis therapy.</p><p><strong>Results: </strong>Sarcopenia was observed in 22 (23.1%) patients. In multiple logistic regression analysis, serum 25(OH)D levels were associated with sarcopenia (odds ratio [OR] 0.87, 95% confidence interval [CI] 0.77-0.99, p = 0.039) independent of traditional risk factors for sarcopenia. In multiple linear regression analyses, serum 25(OH)D levels were associated with parameters of skeletal muscle mass and strength (β = 0.145, p = 0.046, and β = 0.194, p = 0.020, respectively). The adjusted OR for sarcopenia was 5.60 (95% CI 1.52-20.57, p = 0.009) in the vitamin D deficiency group categorized based on the cut-off serum 25(OH)D level of 10 ng/mL. Regarding model discrimination, adding vitamin D deficiency to the traditional risk factors significantly improved the integrated discrimination improvement score (0.093, p = 0.007).</p><p><strong>Conclusion: </strong>Lower serum 25(OH)D levels were associated with sarcopenia independent of traditional risk factors in patients undergoing haemodialysis with suppressed vitamin D activation in the kidney. This finding implies that circulating 25(OH)D may have an important relationship with the skeletal muscle function of patients undergoing haemodialysis, and its measurement may be recommended to identify patients at high risk for sarcopenia among those undergoing haemodialysis.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139680606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2023-09-21DOI: 10.1159/000534106
Heng Shi, Xinhai Zhao, Qin Peng, Xianling Zhou, Sisi Liu, Chuanchuan Sun, Qiuyu Cao, Shiping Zhu, Shengyun Sun
Introduction: Di(2-ethylhexyl) phthalate (DEHP) is a common plasticizer. Studies have revealed that DEHP exposure can cause kidney damage. Green tea is among the most popular beverages in China. Green tea polyphenols (GTPs) have been proven to have therapeutic effects on organ damage induced by heavy metal exposure. However, few studies have reported on GTP-relieving DEHP-induced kidney damage.
Methods: C57BL/6J male mice aged 6-8 weeks were treated with distilled water (control group), 1,500 mg/kg/d DEHP + corn oil (model group), 1,500 mg/kg/d DEHP + corn oil + 70 mg/kg GTP (treatment group), corn oil (oil group), and 70 mg/kg GTP (GTP group) by gavage for 8 weeks, respectively. The renal function of mice and renal tissue histopathology of each group were evaluated. The renal tissues of mice in the model, treatment, and control groups were analyzed using high-throughput sequencing. We calculated the differentially expressed microRNAs (miRNAs) and messenger RNAs (mRNAs) using the limma R package, the CIBERSORT algorithm was used to predict immune infiltration, the starBase database was used to screen the miRNA-mRNA regulatory axis, and immunohistochemical analyses were performed to verify protein expression.
Results: GTP alleviated the deterioration of renal function, renal inflammation and fibrosis, and mitochondrial and endoplasmic reticulum lesions induced by DEHP in mice. Differential immune infiltrations of plasma, dendritic, T, and B cells were noted between the model and treatment groups. We found that three differentially expressed miRNAs (mmu-miR-383-5p, mmu-miR-152-3p, and mmu-miR-144-3p), three differentially expressed mRNAs (Ddit4, Dusp1, and Snx18), and three differentially expressed proteins (Ddit4, Dusp1, and Snx18) played crucial roles in the miRNA-mRNA-protein regulatory axes when GTPs mitigate DEHP-induced kidney damage in mice.
Conclusion: GTP can alleviate DEHP-induced kidney damage and regulate immune cell infiltration. We screened four important miRNA-mRNA-protein regulatory axes of GTP, mitigating DEHP-induced kidney damage in mice.
{"title":"Green Tea Polyphenols Alleviate Kidney Injury Induced by Di(2-Ethylhexyl) Phthalate in Mice.","authors":"Heng Shi, Xinhai Zhao, Qin Peng, Xianling Zhou, Sisi Liu, Chuanchuan Sun, Qiuyu Cao, Shiping Zhu, Shengyun Sun","doi":"10.1159/000534106","DOIUrl":"10.1159/000534106","url":null,"abstract":"<p><strong>Introduction: </strong>Di(2-ethylhexyl) phthalate (DEHP) is a common plasticizer. Studies have revealed that DEHP exposure can cause kidney damage. Green tea is among the most popular beverages in China. Green tea polyphenols (GTPs) have been proven to have therapeutic effects on organ damage induced by heavy metal exposure. However, few studies have reported on GTP-relieving DEHP-induced kidney damage.</p><p><strong>Methods: </strong>C57BL/6J male mice aged 6-8 weeks were treated with distilled water (control group), 1,500 mg/kg/d DEHP + corn oil (model group), 1,500 mg/kg/d DEHP + corn oil + 70 mg/kg GTP (treatment group), corn oil (oil group), and 70 mg/kg GTP (GTP group) by gavage for 8 weeks, respectively. The renal function of mice and renal tissue histopathology of each group were evaluated. The renal tissues of mice in the model, treatment, and control groups were analyzed using high-throughput sequencing. We calculated the differentially expressed microRNAs (miRNAs) and messenger RNAs (mRNAs) using the limma R package, the CIBERSORT algorithm was used to predict immune infiltration, the starBase database was used to screen the miRNA-mRNA regulatory axis, and immunohistochemical analyses were performed to verify protein expression.</p><p><strong>Results: </strong>GTP alleviated the deterioration of renal function, renal inflammation and fibrosis, and mitochondrial and endoplasmic reticulum lesions induced by DEHP in mice. Differential immune infiltrations of plasma, dendritic, T, and B cells were noted between the model and treatment groups. We found that three differentially expressed miRNAs (mmu-miR-383-5p, mmu-miR-152-3p, and mmu-miR-144-3p), three differentially expressed mRNAs (Ddit4, Dusp1, and Snx18), and three differentially expressed proteins (Ddit4, Dusp1, and Snx18) played crucial roles in the miRNA-mRNA-protein regulatory axes when GTPs mitigate DEHP-induced kidney damage in mice.</p><p><strong>Conclusion: </strong>GTP can alleviate DEHP-induced kidney damage and regulate immune cell infiltration. We screened four important miRNA-mRNA-protein regulatory axes of GTP, mitigating DEHP-induced kidney damage in mice.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41098280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2023-10-16DOI: 10.1159/000534608
Louis Baeseman, Samantha Gunning, Jay L Koyner
Background: Sepsis-associated acute kidney injury (AKI) is a leading comorbidity in admissions to the intensive care unit. While a gold standard definition exists, it remains imperfect and does not allow for the timely identification of patients in the setting of critical illness. This review will discuss the use of biochemical and electronic biomarkers to allow for prognostic and predictive enrichment of patients with sepsis-associated AKI over and above the use of serum creatinine and urine output.
Summary: Current data suggest that several biomarkers are capable of identifying patients with sepsis at risk for the development of severe AKI and other associated morbidity. This review discusses these data and these biomarkers in the setting of sub-phenotyping and endotyping sepsis-associated AKI. While not all these tests are widely available and some require further validation, in the near future we anticipate several new tools to help nephrologists and other providers better care for patients with sepsis-associated AKI.
Key messages: Predictive and prognostic enrichment using both traditional biomarkers and novel biomarkers in the setting of sepsis can identify subsets of patients with either similar outcomes or similar pathophysiology, respectively. Novel biomarkers can identify kidney injury in patients without consensus definition AKI (e.g., changes in creatinine or urine output) and can predict other adverse outcomes (e.g., severe consensus definition AKI, inpatient mortality). Finally, emerging artificial intelligence and machine learning-derived risk models are able to predict sepsis-associated AKI in critically ill patients using advanced learning techniques and several laboratory and vital sign measurements.
{"title":"Biomarker Enrichment in Sepsis-Associated Acute Kidney Injury: Finding High-Risk Patients in the Intensive Care Unit.","authors":"Louis Baeseman, Samantha Gunning, Jay L Koyner","doi":"10.1159/000534608","DOIUrl":"10.1159/000534608","url":null,"abstract":"<p><strong>Background: </strong>Sepsis-associated acute kidney injury (AKI) is a leading comorbidity in admissions to the intensive care unit. While a gold standard definition exists, it remains imperfect and does not allow for the timely identification of patients in the setting of critical illness. This review will discuss the use of biochemical and electronic biomarkers to allow for prognostic and predictive enrichment of patients with sepsis-associated AKI over and above the use of serum creatinine and urine output.</p><p><strong>Summary: </strong>Current data suggest that several biomarkers are capable of identifying patients with sepsis at risk for the development of severe AKI and other associated morbidity. This review discusses these data and these biomarkers in the setting of sub-phenotyping and endotyping sepsis-associated AKI. While not all these tests are widely available and some require further validation, in the near future we anticipate several new tools to help nephrologists and other providers better care for patients with sepsis-associated AKI.</p><p><strong>Key messages: </strong>Predictive and prognostic enrichment using both traditional biomarkers and novel biomarkers in the setting of sepsis can identify subsets of patients with either similar outcomes or similar pathophysiology, respectively. Novel biomarkers can identify kidney injury in patients without consensus definition AKI (e.g., changes in creatinine or urine output) and can predict other adverse outcomes (e.g., severe consensus definition AKI, inpatient mortality). Finally, emerging artificial intelligence and machine learning-derived risk models are able to predict sepsis-associated AKI in critically ill patients using advanced learning techniques and several laboratory and vital sign measurements.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10872813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41231687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2023-10-31DOI: 10.1159/000534864
Rima S Zahr, Akram Mohammed, Surabhi Naik, Daniel Faradji, Kenneth I Ataga, Jeffrey Lebensburger, Robert L Davis
Introduction: Acute kidney injury (AKI) is common among hospitalized patients with sickle cell disease (SCD) and contributes to increased morbidity and mortality. Early identification and management of AKI is essential to preventing poor outcomes. We aimed to predict AKI earlier in patients with SCD using a machine-learning model that utilized continuous minute-by-minute physiological data.
Methods: A total of6,278 adult SCD patient encounters were admitted to inpatient units across five regional hospitals in Memphis, TN, over 3 years, from July 2017 to December 2020. From these, 1,178 patients were selected after filtering for data availability. AKI was identified in 82 (7%) patient encounters, using the 2012 Kidney Disease Improving Global Outcomes (KDIGO) criteria. The remaining 1,096 encounters served as controls. Features derived from five physiological data streams, heart rate, respiratory rate, and blood pressure (systolic, diastolic, and mean), captured every minute from bedside monitors were used. An XGBoost classifier was used for classification.
Results: Our model accurately predicted AKI up to 12 h before onset with an area under the receiver operator curve (AUROC) of 0.91 (95% CI [0.89-0.93]) and up to 48 h before AKI with an AUROC of 0.82 (95% CI [0.80-0.83]). Patients with AKI were more likely to be female (64.6%) and have history of hypertension, pulmonary hypertension, chronic kidney disease, and pneumonia than the control group.
Conclusion: XGBoost accurately predicted AKI as early as 12 h before onset in hospitalized SCD patients and may enable the development of innovative prevention strategies.
{"title":"Machine Learning Predicts Acute Kidney Injury in Hospitalized Patients with Sickle Cell Disease.","authors":"Rima S Zahr, Akram Mohammed, Surabhi Naik, Daniel Faradji, Kenneth I Ataga, Jeffrey Lebensburger, Robert L Davis","doi":"10.1159/000534864","DOIUrl":"10.1159/000534864","url":null,"abstract":"<p><strong>Introduction: </strong>Acute kidney injury (AKI) is common among hospitalized patients with sickle cell disease (SCD) and contributes to increased morbidity and mortality. Early identification and management of AKI is essential to preventing poor outcomes. We aimed to predict AKI earlier in patients with SCD using a machine-learning model that utilized continuous minute-by-minute physiological data.</p><p><strong>Methods: </strong>A total of6,278 adult SCD patient encounters were admitted to inpatient units across five regional hospitals in Memphis, TN, over 3 years, from July 2017 to December 2020. From these, 1,178 patients were selected after filtering for data availability. AKI was identified in 82 (7%) patient encounters, using the 2012 Kidney Disease Improving Global Outcomes (KDIGO) criteria. The remaining 1,096 encounters served as controls. Features derived from five physiological data streams, heart rate, respiratory rate, and blood pressure (systolic, diastolic, and mean), captured every minute from bedside monitors were used. An XGBoost classifier was used for classification.</p><p><strong>Results: </strong>Our model accurately predicted AKI up to 12 h before onset with an area under the receiver operator curve (AUROC) of 0.91 (95% CI [0.89-0.93]) and up to 48 h before AKI with an AUROC of 0.82 (95% CI [0.80-0.83]). Patients with AKI were more likely to be female (64.6%) and have history of hypertension, pulmonary hypertension, chronic kidney disease, and pneumonia than the control group.</p><p><strong>Conclusion: </strong>XGBoost accurately predicted AKI as early as 12 h before onset in hospitalized SCD patients and may enable the development of innovative prevention strategies.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10872356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71419735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Hepatitis B virus (HBV) infection is prevalent in Asia including Taiwan. We retrospectively evaluated the risk of HBV reactivation and clinical outcomes in HBV+ and HBV- kidney transplant recipients.
Methods: Patients who underwent kidney transplantation between January 2004 and December 2021 were reviewed. The outcomes of interest included risks of HBV reactivation and patient/graft survival.
Results: We identified 337 patients (47.5 ± 12 years) in our final cohort. Fifty-two (15.4%) had hepatitis B surface antigen (HBsAg) positive at the time of transplantation. Seventeen developed viral reactivations, with 41.2% of them accompanied by active hepatitis. The graft survival, acute rejection rate, and cancer development after kidney transplantation did not differ in terms of HBsAg status. The Cox multivariate analysis indicated the HBV reactivation risk was increased by a lack of pretransplant anti-HBV medication (hazard ratio [HR], 5.95; 95% confidence interval [CI], 1.31-27.02; p = 0.021) or an absence of lifelong antiviral therapy (HR: 3.14; 95% CI: 1.01-9.74; p = 0.047).
Conclusion: Individuals, independent of HBsAg status, had similar prognosis in terms of patient and graft survival, acute rejection rate, and cancer development. The absence of either pretransplant anti-HBV medication or lifelong antiviral therapy was significantly associated with an increased risk of HBV reactivation.
{"title":"The Risk Factors and Clinical Outcomes in Hepatitis B Seropositive and Seronegative Renal Transplant Patients.","authors":"Yu-Lien Tsai, Meng-Hsuan Chung, Niang-Cheng Lin, Cheng-Yen Chen, Yao-Ping Lin, Ming-Tsun Tsai, Hsin-Lin Tsai, Yee-An Chen, Shuo-Ming Ou, Chi-Jen Chu, Tsai-Hung Wu, Chang-Youh Tsai","doi":"10.1159/000538231","DOIUrl":"10.1159/000538231","url":null,"abstract":"<p><strong>Introduction: </strong>Hepatitis B virus (HBV) infection is prevalent in Asia including Taiwan. We retrospectively evaluated the risk of HBV reactivation and clinical outcomes in HBV+ and HBV- kidney transplant recipients.</p><p><strong>Methods: </strong>Patients who underwent kidney transplantation between January 2004 and December 2021 were reviewed. The outcomes of interest included risks of HBV reactivation and patient/graft survival.</p><p><strong>Results: </strong>We identified 337 patients (47.5 ± 12 years) in our final cohort. Fifty-two (15.4%) had hepatitis B surface antigen (HBsAg) positive at the time of transplantation. Seventeen developed viral reactivations, with 41.2% of them accompanied by active hepatitis. The graft survival, acute rejection rate, and cancer development after kidney transplantation did not differ in terms of HBsAg status. The Cox multivariate analysis indicated the HBV reactivation risk was increased by a lack of pretransplant anti-HBV medication (hazard ratio [HR], 5.95; 95% confidence interval [CI], 1.31-27.02; p = 0.021) or an absence of lifelong antiviral therapy (HR: 3.14; 95% CI: 1.01-9.74; p = 0.047).</p><p><strong>Conclusion: </strong>Individuals, independent of HBsAg status, had similar prognosis in terms of patient and graft survival, acute rejection rate, and cancer development. The absence of either pretransplant anti-HBV medication or lifelong antiviral therapy was significantly associated with an increased risk of HBV reactivation.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140157312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2024-03-29DOI: 10.1159/000538253
Dustin Le, Deidra C Crews, Morgan E Grams, Josef Coresh, Jung-Im Shin
Introduction: Case reports have suggested a causative role between sevelamer use and subsequent gastrointestinal bleeding (GIB), but no large observational studies have evaluated this association.
Methods: Using the United States Renal Data System database from 2015 to 2019, we examined the association between initiation of sevelamer (vs. non-sevelamer containing phosphate binders) and GIB hospitalization as well as all-cause mortality among individuals on hemodialysis. We emulated a target trial using Cox regression models and inverse probability of treatment weights to estimate the adjusted hazard ratios (HR) across outcomes and subgroups.
Results: Among 21,354 new users of phosphate binders (11,276 sevelamer and 10,078 non-sevelamer) with baseline lab data (calcium, phosphorus, hemoglobin, and albumin), there were 2,811 GIB hospitalizations and 5,920 deaths after a median follow-up of 1.3 years. Compared with the initiation of non-sevelamer binders, sevelamer was not associated with an increased risk of GIB hospitalization (89 vs. 90 events per 1,000 person-years; IPTW-HR: 0.98, 95% CI: 0.91-1.06) or all-cause mortality (220 vs. 224 events per 1,000 person-years; IPTW-HR: 0.98, 95% CI: 0.93-1.03). Subgroup analyses (such as diabetes and anti-coagulation use) were generally consistent, and there was no association between sevelamer dose and GIB hospitalization.
Conclusion: Among patients requiring hemodialysis, sevelamer (vs. non-sevelamer) containing phosphate binders was not associated with increased risk of GIB hospitalization.
{"title":"Association of Sevelamer Initiation with Gastrointestinal Bleeding Hospitalization in Individuals Requiring Hemodialysis.","authors":"Dustin Le, Deidra C Crews, Morgan E Grams, Josef Coresh, Jung-Im Shin","doi":"10.1159/000538253","DOIUrl":"10.1159/000538253","url":null,"abstract":"<p><strong>Introduction: </strong>Case reports have suggested a causative role between sevelamer use and subsequent gastrointestinal bleeding (GIB), but no large observational studies have evaluated this association.</p><p><strong>Methods: </strong>Using the United States Renal Data System database from 2015 to 2019, we examined the association between initiation of sevelamer (vs. non-sevelamer containing phosphate binders) and GIB hospitalization as well as all-cause mortality among individuals on hemodialysis. We emulated a target trial using Cox regression models and inverse probability of treatment weights to estimate the adjusted hazard ratios (HR) across outcomes and subgroups.</p><p><strong>Results: </strong>Among 21,354 new users of phosphate binders (11,276 sevelamer and 10,078 non-sevelamer) with baseline lab data (calcium, phosphorus, hemoglobin, and albumin), there were 2,811 GIB hospitalizations and 5,920 deaths after a median follow-up of 1.3 years. Compared with the initiation of non-sevelamer binders, sevelamer was not associated with an increased risk of GIB hospitalization (89 vs. 90 events per 1,000 person-years; IPTW-HR: 0.98, 95% CI: 0.91-1.06) or all-cause mortality (220 vs. 224 events per 1,000 person-years; IPTW-HR: 0.98, 95% CI: 0.93-1.03). Subgroup analyses (such as diabetes and anti-coagulation use) were generally consistent, and there was no association between sevelamer dose and GIB hospitalization.</p><p><strong>Conclusion: </strong>Among patients requiring hemodialysis, sevelamer (vs. non-sevelamer) containing phosphate binders was not associated with increased risk of GIB hospitalization.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140331390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}