Juan A Medaura, Meijiao Zhou, Linda H Ficociello, Michael S Anger, Stuart M Sprague
{"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":" ","pages":"127-135"},"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}
Heng Shi, Xinhai Zhao, Qin Peng, Xianling Zhou, Sisi Liu, Chuanchuan Sun, Qiuyu Cao, Shiping Zhu, Shengyun Sun
{"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":" ","pages":"86-105"},"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}
{"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":" ","pages":"72-85"},"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}
Rima S Zahr, Akram Mohammed, Surabhi Naik, Daniel Faradji, Kenneth I Ataga, Jeffrey Lebensburger, Robert L Davis
{"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":" ","pages":"18-24"},"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}
{"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":" ","pages":"477-486"},"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}
Dustin Le, Deidra C Crews, Morgan E Grams, Josef Coresh, Jung-Im Shin
{"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":" ","pages":"450-462"},"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}
Elena Rodriguez-Sanchez, Jennifer Aceves-Ripoll, Elisa Mercado-García, José A Navarro-García, Amado Andrés, José M Aguado, Julián Segura, Luis M Ruilope, Mario Fernández-Ruiz, Gema Ruiz-Hurtado
{"title":"Donor-Dependent Variations in Systemic Oxidative Stress and Their Association with One-Year Graft Outcomes in Kidney Transplantation.","authors":"Elena Rodriguez-Sanchez, Jennifer Aceves-Ripoll, Elisa Mercado-García, José A Navarro-García, Amado Andrés, José M Aguado, Julián Segura, Luis M Ruilope, Mario Fernández-Ruiz, Gema Ruiz-Hurtado","doi":"10.1159/000539509","DOIUrl":"10.1159/000539509","url":null,"abstract":"<p><strong>Introduction: </strong>Oxidative stress has been implicated in complications after kidney transplantation (KT), including delayed graft function (DGF) and rejection. However, its role in long-term posttransplant outcomes remains unclear.</p><p><strong>Methods: </strong>We investigated oxidative damage and antioxidant defense dynamics, and their impact on the graft outcomes, in 41 KT recipients categorized by type of donation over 12 months. Oxidative status was determined using OxyScore and AntioxyScore indexes, which comprise several circulating biomarkers of oxidative damage and antioxidant defense. Donor types included donation after brain death (DBD [61.0%]), donation after circulatory death (DCD [26.8%]), and living donation (LD [12.1%]).</p><p><strong>Results: </strong>There was an overall increase in oxidative damage early after transplantation, which was significantly higher in DCD as compared to DBD and LD recipients. The multivariate adjustment confirmed the independent association of OxyScore and type of deceased donation with DGF, donor kidney function, and induction therapy with antithymocyte globulin. There were no differences in terms of antioxidant defense. Lower oxidative damage at day 7 predicted better graft function at 1-year posttransplant only in DBD recipients.</p><p><strong>Conclusion: </strong>DCD induced greater short-term oxidative damage after KT, whereas the early levels of oxidative damage were predictive of the graft function 1 year after KT among DBD recipients.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"509-519"},"PeriodicalIF":4.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141299782","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}
Amy S You, Keith C Norris, Merle Kataoka-Yahiro, James Davis, Victoria Page, Glen Hayashida, Yoko Narasaki, Shiuh Feng Cheng, Roland Ng, Linda L Wong, Lung-Yi Lee, Kamyar Kalantar-Zadeh, Connie M Rhee
{"title":"Racial Disparities in End-Stage Kidney Disease Outcomes among Asians and Native Hawaiians and Other Pacific Islanders across Geographic Residence.","authors":"Amy S You, Keith C Norris, Merle Kataoka-Yahiro, James Davis, Victoria Page, Glen Hayashida, Yoko Narasaki, Shiuh Feng Cheng, Roland Ng, Linda L Wong, Lung-Yi Lee, Kamyar Kalantar-Zadeh, Connie M Rhee","doi":"10.1159/000534052","DOIUrl":"10.1159/000534052","url":null,"abstract":"<p><strong>Introduction: </strong>While Asian and Native Hawaiian and other Pacific Islander (NHOPI) patients have a high prevalence of kidney disease risk factors, there are sparse data examining their end-stage kidney disease (ESKD) outcomes. As Hawaii has high representation of Asian and NHOPI individuals, we compared their ESKD outcomes based on residence in the mainland USA versus Hawaii/Pacific Islands (PIs).</p><p><strong>Materials and methods: </strong>Using United States Renal Data System data, we examined the impact of geographic residence in the mainland versus Hawaii/PIs on race-mortality associations among incident ESKD patients transitioning to dialysis over January 1, 2000-December 31, 2016 using Cox regression. We examined likelihood of post-dialysis kidney transplantation using Cox models and cumulative incidence curves.</p><p><strong>Results: </strong>Compared with White patients in the mainland, Asian and NHOPI patients in the mainland had lower mortality: adjusted HRs (95% CIs) 0.67 (0.66-0.67) and 0.72 (0.70-0.73), respectively. When examining Asian and NHOPI patients in Hawaii/PIs, survival benefit was attenuated in Asian and diminished to the null in NHOPI patients (ref: mainland White patients). Cumulative incidence curves comparing Asian, NHOPI, and White patients showed Asian and NHOPI patients in the mainland had the highest likelihood of transplantation, whereas NHOPI and Asian patients in Hawaii/PIs had the lowest likelihood.</p><p><strong>Conclusion: </strong>In the mainland, Asian and NHOPI patients had lower mortality versus White patients, whereas in Hawaii/PIs, this survival benefit was diminished in Asian and mitigated in NHOPI patients. NHOPI and Asian patients in Hawaii/PIs had less transplantation versus those in the mainland. Further research is needed to uncover factors contributing to differential ESKD outcomes among Asian and NHOPI patients across geographic residence.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"115-126"},"PeriodicalIF":4.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41110622","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}
{"title":"Sickle Cell Disease and CKD: An Update.","authors":"Rima S Zahr, Santosh L Saraf","doi":"10.1159/000534865","DOIUrl":"10.1159/000534865","url":null,"abstract":"<p><strong>Background: </strong>Sickle cell disease is an inherited red blood cell disorder that affects approximately 100,000 people in the USA and 25 million people worldwide. Vaso-occlusion and chronic hemolysis lead to dysfunction of vital organ systems, with the kidneys being among the most commonly affected organs.</p><p><strong>Summary: </strong>Early renal manifestations include medullary ischemia with the loss of urine-concentrating ability and hyperfiltration. This can be followed by progressive damage characterized by persistent albuminuria and a decline in the estimated glomerular filtration rate. The risk of sickle nephropathy is greater in those with the APOL1 G1 and G2 kidney risk variants and variants in HMOX1 and lower in those that coinherit α-thalassemia. Therapies to treat sickle cell disease-related kidney damage focus on sickle cell disease-modifying therapies (e.g., hydroxyurea) or those adopted from the nonsickle cell disease kidney literature (e.g., renin-angiotensin-aldosterone system inhibitors), although data on their clinical efficacy are limited to small studies with short follow-up periods. Kidney transplantation for end-stage kidney disease improves survival compared to hemodialysis but is underutilized in this patient population.</p><p><strong>Key messages: </strong>Kidney disease is a major contributor to early mortality, and more research is needed to understand the pathophysiology and develop targeted therapies to improve kidney health in sickle cell disease.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"56-71"},"PeriodicalIF":4.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10872505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71410203","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}
Natalie Gendy, Liam Brown, Mary Kate Staunton, Kanika Garg, Nora Hernandez Garcilazo, Long Qian, Yu Yamamoto, Ugochukwu Ugwuowo, Wassim Obeid, Lama Al-Qusairi, Andrew Bostom, Sherry G Mansour
{"title":"The Role of Angiopoietins in Cardiovascular Outcomes of Kidney Transplant Recipients: An Ancillary Study from the FAVORIT.","authors":"Natalie Gendy, Liam Brown, Mary Kate Staunton, Kanika Garg, Nora Hernandez Garcilazo, Long Qian, Yu Yamamoto, Ugochukwu Ugwuowo, Wassim Obeid, Lama Al-Qusairi, Andrew Bostom, Sherry G Mansour","doi":"10.1159/000538878","DOIUrl":"10.1159/000538878","url":null,"abstract":"<p><strong>Introduction: </strong>Kidney transplant recipients (KTRs) have increased risk of cardiovascular disease (CVD) mortality. We investigated vascular biomarkers, angiopoietin-1, and angiopoietin-2 (angpt-1, -2), in CVD development in KTRs.</p><p><strong>Methods: </strong>This ancillary study from the FAVORIT evaluates the associations of baseline plasma angpt-1, -2 levels in CVD development (primary outcome) and graft failure (GF) and death (secondary outcomes) in 2000 deceased donor KTRs. We used Cox regression to analyze the association of biomarker quartiles with outcomes. We adjusted for demographic; CVD- and transplant-related variables; medications; urine albumin-to-creatinine ratio; and randomization status. We calculated areas under the curves (AUCs) to predict CVD or death, and GF or death by incorporating biomarkers alongside clinical variables.</p><p><strong>Results: </strong>Participants' median age was 52 IQR [45, 59] years: with 37% women and 73% identifying as white. Median time from transplantation was 3.99 IQR [1.58, 7.93] years and to CVD development was 2.54 IQR [1.11-3.80] years. Quartiles of angpt-1 were not associated with outcomes. Whereas higher levels of angpt-2 (quartile 4) were associated with about 2 times the risk of CVD, GF, and death (aHR 1.85 [1.25-2.73], p < 0.01; 2.24 [1.36-3.70)], p < 0.01; 2.30 [1.48-3.58], p < 0.01, respectively) as compared to quartile 1. Adding angiopoietins to preexisting clinical variables improved prediction of CVD or death (AUC improved from 0.70 to 0.72, p = 0.005) and GF or death (AUC improved from 0.68 to 0.70, p = 0.005). Angpt-2 may partially explain the increased risk of future CVD in KTRs. Further research is needed to assess the utility of using angiopoietins in the clinical care of KTRs.</p><p><strong>Conclusion: </strong>Angpt-2 may be a useful prognostic tool for future CVD in KTRs. Combining angiopoietins with clinical markers may tailor follow-up to mitigate CVD risk.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"597-606"},"PeriodicalIF":4.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11444892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140911542","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}