American Journal of Nephrology最新文献

{"title":"Autonomic Nervous System Dysfunction in Peritoneal Dialysis Patients: An Underrecognized Cardiovascular Risk Factor?","authors":"Danai Faitatzidou, Artemios G Karagiannidis, Marieta P Theodorakopoulou, Andrew Xanthopoulos, Filippos Triposkiadis, Pantelis A Sarafidis","doi":"10.1159/000534318","DOIUrl":"10.1159/000534318","url":null,"abstract":"<p><strong>Background: </strong>In patients with end-stage kidney disease (ESKD) receiving peritoneal dialysis (PD), cardiovascular events represent the predominant cause of morbidity and mortality, with cardiac arrhythmias and sudden death being the leading causes of death in this population. Autonomic nervous system (ANS) dysfunction is listed among the non-traditional risk factors accounting for the observed high cardiovascular burden, with a plethora of complex and not yet fully understood pathophysiologic mechanisms being involved.</p><p><strong>Summary: </strong>In recent years, preliminary studies have investigated and confirmed the presence of ANS dysfunction in PD patients, while relevant results from cohort studies have linked ANS dysfunction with adverse clinical outcomes in these patients. In light of these findings, ANS dysfunction has been recently receiving wider consideration as an independent cardiovascular risk factor in PD patients. The aim of this review was to describe the mechanisms involved in the pathogenesis of ANS dysfunction in ESKD and particularly PD patients and to summarize the existing studies evaluating ANS dysfunction in PD patients.</p><p><strong>Key messages: </strong>ANS dysfunction in PD patients is related to multiple complex mechanisms that impair the balance between SNS/PNS, and this disruption represents a crucial intermediator of cardiovascular morbidity and mortality in this population.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"37-55"},"PeriodicalIF":4.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41111552","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":"Nocturnal Hemodynamics in Somali Americans: Implications for Cardiovascular Risk.","authors":"Ian M Greenlund, Dimitrios Kantas, Sakthi Surya Prakash, Joshua M Bock, Naima Covassin, Virend K Somers","doi":"10.1159/000540987","DOIUrl":"10.1159/000540987","url":null,"abstract":"<p><strong>Introduction: </strong>Cardiovascular health disparities are present within several minority communities, but it is unclear if such disparities are present in a growing African American subpopulation, Somali Americans, who differ genetically and culturally from African Americans of Western African ancestry. Ambulatory blood pressure (BP) monitoring remains a gold standard measure to examine 24-h BP patterns to stratify cardiovascular risk profile. We sought to examine differences in the 24-h BP profile in a sample of young Somali Americans and compare their BP patterns to White study participants. We hypothesized that their BP and heart rate (HR) would be higher compared to closely matched White participants.</p><p><strong>Methods: </strong>We recruited 50 participants (25 Somali) in whom BP recordings were obtained every 20 min throughout the entire 24-h monitoring period to quantify BP, HR, and ambulatory arterial stiffness. Daytime BP/HR was quantified between 10:00 a.m. and 8:00 p.m., and nighttime BP/HR was assessed between 12:00 a.m. and 6:00 a.m.</p><p><strong>Results: </strong>Daytime BP and HR were similar between racial groups (p > 0.05). Nighttime BP was similar between groups (p > 0.05), but Somali American individuals exhibited a higher nocturnal HR compared to White participants (p = 0.013). Nocturnal dipping in diastolic BP and HR dipping was attenuated in Somali Americans compared to White adults (p = 0.038, 0.007). Somali participants also had higher ambulatory arterial stiffness (p = 0.045).</p><p><strong>Conclusion: </strong>Twenty four-hour hemodynamics, specifically ambulatory arterial stiffness, nocturnal BP, and nocturnal HR, differ in young Somali Americans compared to White adults. These findings provide new insight into potential cardiovascular health disparities and future cardiovascular risk within the burgeoning Somali American community.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"629-637"},"PeriodicalIF":4.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054655","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":"Patiromer-Facilitated Renin-Angiotensin-Aldosterone System Inhibitor Utilization in Patients with Heart Failure with or without Comorbid Chronic Kidney Disease: Subgroup Analysis of DIAMOND Randomized Trial.","authors":"Matthew R Weir, Patrick Rossignol, Bertram Pitt, Lars H Lund, Andrew J S Coats, Gerasimos Filippatos, Amandine Perrin, Sandra Waechter, Jeffrey Budden, Mikhail Kosiborod, Marco Metra, Michael Boehm, Justin A Ezekowitz, Antoni Bayes-Genis, Robert J Mentz, Piotr Ponikowski, Michele Senni, Eliodoro Castro-Montes, Jose Carlos Nicolau, Alexandr Parkhomenko, Petar Seferovic, Alain Cohen-Solal, Stefan D Anker, Javed Butler","doi":"10.1159/000540453","DOIUrl":"10.1159/000540453","url":null,"abstract":"<p><strong>Introduction: </strong>Renin-angiotensin-aldosterone system inhibitor (RAASi; including mineralocorticoid receptor antagonists [MRAs]) benefits are greatest in patients with heart failure with reduced ejection fraction (HFrEF) and chronic kidney disease (CKD); however, the risk of hyperkalemia (HK) is high.</p><p><strong>Methods: </strong>The DIAMOND trial (NCT03888066) assessed the ability of patiromer to control serum potassium (sK+) in patients with HFrEF with/without CKD. Prior to randomization (double-blind withdrawal, 1:1), patients on patiromer had to achieve ≥50% recommended doses of RAASi and 50 mg/day of MRA with normokalemia during a run-in period. The present analysis assessed the effect of baseline estimated glomerular filtration rate (eGFR) in subgroups of ≥/<60, ≥/<45 (prespecified), and ≥/<30 mL/min/1.73 m2 (added post hoc).</p><p><strong>Results: </strong>In total, 81.3, 78.9, and 81.1% of patients with eGFR <60, <45, and <30 mL/min/1.73 m2 at screening achieved RAASi/MRA targets. A greater efficacy of patiromer versus placebo to control sK+ in patients with more advanced CKD was reported (p-interaction ≤ 0.027 for all eGFR subgroups). Greater effects on secondary endpoints were observed with patiromer versus placebo in patients with eGFR <60 and <45 mL/min/1.73 m2. Adverse effects were similar between patiromer and placebo across subgroups.</p><p><strong>Conclusion: </strong>Patiromer enabled use of RAASi, controlled sK+, and minimized HK risk in patients with HFrEF, with greater effect sizes for most endpoints noted in patient subgroups with lower eGFR. Patiromer was well tolerated by patients in all eGFR subgroups.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"672-689"},"PeriodicalIF":4.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003386","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":"Difelikefalin in Black/African American Hemodialysis Patients with Moderate-to-Severe Pruritus: Post hoc Analysis of KALM-1 and KALM-2.","authors":"Steven Fishbane, Deborah J Clegg, Edgar V Lerma, Anjay Rastogi, Jeffrey Budden, Isabelle Morin, Warren Wen, Frédérique Menzaghi, Joel Topf","doi":"10.1159/000534227","DOIUrl":"10.1159/000534227","url":null,"abstract":"<p><strong>Introduction: </strong>Black and African American (AA) people are over-represented in the kidney failure population; therefore, the safety and efficacy of difelikefalin in Black/AA patients was evaluated.</p><p><strong>Methods: </strong>This was a post hoc, pooled exploratory subgroup analysis of the Phase 3 KALM-1 and -2 studies. Patients undergoing hemodialysis (HD) who had moderate-to-severe chronic kidney disease-associated pruritus (CKD-aP) at enrollment were stratified into self-reported Black/AA or White subgroups. Patients were randomized (1:1) to receive intravenous (IV) difelikefalin 0.5 µg/kg or placebo for 12 weeks. Difelikefalin efficacy was assessed with validated patient-reported outcome questionnaires: 24-h Worst Itch Numerical Rating Scale (WI-NRS), 5-D itch, and Skindex‑10.</p><p><strong>Results: </strong>There were 249 (29.3%) patients from the KALM studies that self-identified as Black/AA (n = 135 difelikefalin; n = 114 placebo). Clinically meaningful (≥3-point) reduction in WI-NRS score was achieved by 47.9% of Black/AA patients with difelikefalin versus 24.6% with placebo (p &lt; 0.001). More Black/AA patients achieved a ≥5-point 5-D itch total improvement (54.9% vs. 35.7%; p = 0.013) and a ≥15-point Skindex-10 score improvement with difelikefalin versus placebo (49.0% vs. 28.9%; p = 0.006) compared with White patients. Incidence of treatment-emergent adverse events (TEAEs) was higher for Black/AA patients (difelikefalin: 78.5%; placebo: 70.8%) versus White patients (difelikefalin: 64.8%; placebo: 61.8%).</p><p><strong>Conclusion: </strong>In this post hoc analysis, difelikefalin was efficacious in the Black/AA population and had an acceptable safety profile.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"329-333"},"PeriodicalIF":4.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11152003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139519480","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":"Diabetic Retinopathy and Chronic Kidney Disease: Associations and Comorbidities in a Large Diabetic Population - The Tongren Health Care Study.","authors":"Li Qin Gao, Can Can Xue, Jing Cui, Jie Xu, Chun Zhang, Dong Ning Chen, Jost B Jonas, Ya Xing Wang","doi":"10.1159/000535059","DOIUrl":"10.1159/000535059","url":null,"abstract":"<p><strong>Introduction: </strong>The aim of the study was to investigate associations between diabetic retinopathy (DR) and chronic kidney disease (CKD) in patients with type 2 diabetes (TD2).</p><p><strong>Methods: </strong>The participants of the cross-sectional, community-based Tongren Health Care Study underwent a detailed medical and ophthalmological examination. We defined TD2 by a fasting plasma glucose concentration of ≥7.0 mmol/L or a medical history. CKD was classified as either reduced estimated glomerular filtration rate (eGFR) of &lt;60 mL/min/1.73 mm2 or presence of albuminuria. DR was assessed using color fundus photographs.</p><p><strong>Results: </strong>Out of 62,217 participants of the Tongren Health Care Study, 5,103 (8.2%) patients had TD2. The prevalence of DR was 12.8% (95% CI, 11.8%, 13.7%), CKD was 13.3% (95% CI, 12.4%, 14.3%), and the subtypes of CKD including reduced eGFR and albuminuria was 4.6% (95% CI, 4.2%, 5.1%) and 10.1% (95% CI, 9.3%, 10.9%), respectively. DR was detectable in 21.0% of the patients with CKD, while CKD was present in 20.9% of the DR patients. Higher DR prevalence was associated with higher prevalence of albuminuria and reduced eGFR (both p &lt; 0.05). Factors independently associated with the presence of CKD instead of DR were older age (p &lt; 0.001, OR = 1.05), a higher body mass index (p &lt; 0.001, OR = 1.14), a higher serum concentration of triglycerides (p &lt; 0.001, OR = 1.26), and a lower blood glucose (p &lt; 0.001, OR = 0.93). Having hypertension was additionally associated with the presence of reduced eGFR as compared with DR (p = 0.005, OR = 4.47).</p><p><strong>Conclusions: </strong>TD2 patients of older age and with higher body mass index, hypertension, and dyslipidemia had a higher probability of being affected by CKD rather than DR, while those with a higher blood glucose level were more prone to DR than CKD.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"175-186"},"PeriodicalIF":4.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89716653","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":"Efficacy of Rituximab for Minimal Change Disease and Focal Segmental Glomerulosclerosis with Frequently Relapsing or Steroid-Dependent Nephrotic Syndrome in Adults: A Chinese Multicenter Retrospective Study.","authors":"Lan Lan, Yuxin Lin, Binfeng Yu, Yin Wang, Hong Pan, Huijing Wang, Xiaowei Lou, Xiabing Lang, Qiankun Zhang, Lie Jin, Yi Yang, Liang Xiao, Jianghua Chen, Fei Han","doi":"10.1159/000535010","DOIUrl":"10.1159/000535010","url":null,"abstract":"<p><strong>Introduction: </strong>Rituximab has been proven effective and safe in pediatric patients with frequently relapsing or steroid-dependent nephrotic syndrome (FR/SDNS). We aimed to analyze the efficacy and safety of rituximab in adult FR/SDNS patients with minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS).</p><p><strong>Methods: </strong>A retrospective cohort study at three nephrology centers in China included adult FR/SDNS patients with biopsy-proven MCD or FSGS. Primary outcomes were relapse frequency and first relapse-free survival time. Adverse events were well recorded, and logistic regression analyses were used to investigate the risk factors of relapse.</p><p><strong>Results: </strong>Eighty-one patients (age, 25.0 years; interquartile range, 20.0-40.5; 67% males; 82.7% MCD) received an average rituximab dose of 1,393.8 ± 618.7 mg/2 years during the 2-year follow-up period. The relapse frequency, calculated as the ratio of relapse times to follow-up years, significantly decreased after rituximab treatment (0.04 [0.00, 0.08] vs. 1.71 [1.00, 2.45], p &lt; 0.001). The first relapse-free survival time was 16.7 ± 8.0 months. Fifty-seven patients (70.4%) achieved cessation of corticosteroids and immunosuppressants within 3 months after the first rituximab infusion. Adverse events were mostly mild, and no severe treatment-related adverse events were observed. Low serum albumin level before rituximab and high CD56+CD16+ natural killer cell count after rituximab were independent risk factors of relapse within 2 years after rituximab treatment.</p><p><strong>Conclusion: </strong>Rituximab was proven an effective and safe treatment option for adult FR/SDNS patients with MCD or FSGS in maintaining disease remission and minimizing corticosteroid exposure.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"25-36"},"PeriodicalIF":4.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"107589975","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":"Impact of Fat Mass on Osteoporosis, Sarcopenia, and Osteosarcopenia in Peritoneal Dialysis Patients.","authors":"In Soo Kim, Hyung Seok Lee, Jinha Jang, Jung Nam An, Sung Gyun Kim, Jwa-Kyung Kim","doi":"10.1159/000540948","DOIUrl":"10.1159/000540948","url":null,"abstract":"<p><strong>Introduction: </strong>The relationship between fat mass and osteoporosis, sarcopenia, and osteosarcopenia is complex. While higher fat mass generally has a negative impact on bone and muscle health in the general population, the impact in peritoneal dialysis (PD) patients is less well understood.</p><p><strong>Methods: </strong>In this study of 359 PD patients, sarcopenia was identified using appendicular skeletal muscle per square meter (ASM/m2), with cut-off values of <7.0 kg/m2 for men and <5.5 kg/m2 for women. Fat tissue index (FTI) and lean tissue index (LTI) were determined using body composition monitoring, with the lowest tertile classified as low FTI and low LTI. Bone mineral density was measured, with a T-score below -2.5 indicating osteoporosis.</p><p><strong>Results: </strong>The prevalence of osteoporosis, sarcopenia, and osteosarcopenia was 25%, 32%, and 15%, respectively. Notably, 60% of osteoporotic patients had sarcopenia, and about 45% of sarcopenic patients had osteoporosis. Patients with osteoporosis were older and had significantly lower LTI (15.3 vs. 12.7 kg/m2, p < 0.001) and ASM (7.3 vs. 5.8 kg/m2, p < 0.001). Osteoporotic patients also had lower FTI, but this was more pronounced in men than in women. Patients with both sarcopenia and osteoporosis had the lowest LTI and FTI compared to those with only one or neither condition. Low FTI was a significant determinant for osteoporosis (OR, 2.34; 95% CI, 1.43-3.85; p = 0.001), sarcopenia (OR, 2.91; 95% CI, 1.82-4.64; p < 0.001), and osteosarcopenia (OR, 2.34; 95% CI, 1.30-4.24; p = 0.005) in univariate analysis, and these associations remained significant after adjustment for age and body mass index.</p><p><strong>Conclusion: </strong>Osteoporosis and sarcopenia are common and interrelated in PD patients. Low fat mass, but not normal/high fat mass, was significantly associated with these conditions, suggesting the importance of maintaining adequate fat mass in PD patients.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"607-617"},"PeriodicalIF":4.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999278","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":"C4d, rather than C3d and C5b-9, Is Associated with Graft Loss in Recurrent IgA Deposition after Kidney Transplantation.","authors":"Firas F Alkaff, Audrey Uffing, Gesa Tiller, Rosa G M Lammerts, Marius C van den Heuvel, Ingeborg M Bajema, Mohamed R Daha, Jacob van den Born, Stefan P Berger","doi":"10.1159/000540986","DOIUrl":"10.1159/000540986","url":null,"abstract":"<p><strong>Introduction: </strong>Recurrent IgA deposition is common after kidney transplantation. However, it is difficult to define whether IgA deposition is innocuous or contributes to organ damage. Next, although complement is known to be involved in the pathogenesis of IgA nephropathy (IgAN), its involvement has not been studied systematically in kidney transplant recipients (KTRs).</p><p><strong>Methods: </strong>KTRs with biopsy-proven native IgAN who underwent kidney biopsy after transplantation between 1995 and 2020 were included. Recurrent IgA deposition was defined as IgA deposit in the glomerulus. Staining of complement factors C4d, C3d, and C5b-9 was quantitatively evaluated using ImageScope.</p><p><strong>Results: </strong>Sixty-seven KTRs (85% male, 46 ± 13 years old, 12 [6-24] months after transplantation, 58% with indication biopsy) were included in the analyses. Of them, 25 (37%) had recurrent IgA deposition. There were no clinical differences between KTR with and without recurrent IgA deposition. C3d and C5b-9 were always present in biopsies with IgA deposition, while C4d was present in 48% of the biopsies. During a median follow-up of 9.6 [4.8-14] years, 18 (27%) KTRs developed death-censored graft failure. Recurrent IgA deposition was not associated with graft failure. Of the evaluated complement factors, only C4d staining was associated with graft failure in KTR with recurrent IgA deposition (hazard ratio = 2.55, 95% confidence interval = 1.07-6.03, p = 0.034).</p><p><strong>Conclusions: </strong>Recurrent IgA deposition was not associated with graft failure in itself. C4d, when present, is strongly associated with graft loss in KTR with recurrent IgA deposition, suggesting a pathogenic role for the lectin pathway in recurrent IgAN.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"690-699"},"PeriodicalIF":4.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999277","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":"Association between Timing of Vascular Access Creation and Mortality in Patients Initiating Hemodialysis: A Nationwide Cohort Study in Japan.","authors":"Minoru Murakami, Naohiko Fujii, Eiichiro Kanda, Kan Kikuchi, Atsushi Wada, Takayuki Hamano, Ikuto Masakane","doi":"10.1159/000541356","DOIUrl":"10.1159/000541356","url":null,"abstract":"<p><strong>Introduction: </strong>The optimal time for vascular access (VA) creation remains controversial.</p><p><strong>Methods: </strong>We conducted a cohort study using data from the Japanese Society for Dialysis Therapy Renal Data Registry. Adult patients who started receiving hemodialysis in 2007 and had a permanent VA created were included. The exposure of interest was the timing of VA creation, categorized into three groups: early VA creation (defined as creation at least 4 months before hemodialysis initiation), just prior VA creation (creation between 1 and 3 months before hemodialysis initiation), and late VA creation (creation within 1 month of or after hemodialysis initiation). Cox regression analyses were used to compare 1-year all-cause mortality, with late VA creation as the reference group. Owing to the violations of the proportional hazards assumptions, the follow-up period was divided into \"early\" (1-4 months follow-up) and \"late\" (5-12 months follow-up) periods.</p><p><strong>Results: </strong>Overall, 1,280 (15.4%) of 8,322 patients died. Both early creation and just prior creation were associated with lower all-cause mortality in the early period compared with late creation. In the late period, the hazard ratios (HRs) for all-cause mortality decreased with earlier VA creation (adjusted HRs [95% confidence intervals]: 0.49 [0.35-0.67] for the early creation group and 0.63 [0.51-0.79] for the just prior creation group).</p><p><strong>Conclusion: </strong>Our study suggests that VA creation at least 1 month before hemodialysis initiation is associated with lower all-cause mortality in the early period, with earlier VA creation resulting in further mortality reduction in the late period.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"647-656"},"PeriodicalIF":4.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153022","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":"Mechanistic and Clinical Comparison of the Erythropoietic Effects of SGLT2 Inhibitors and Prolyl Hydroxylase Inhibitors in Patients with Chronic Kidney Disease and Renal Anemia.","authors":"Milton Packer","doi":"10.1159/000531084","DOIUrl":"10.1159/000531084","url":null,"abstract":"<p><p>Renal anemia is treated with erythropoiesis-stimulating agents (ESAs), even though epoetin alfa and darbepoetin increase the risk of cardiovascular death and thromboembolic events, including stroke. Hypoxia-inducible factor prolyl hydroxylase domain (HIF-PHD) inhibitors have been developed as an alternative to ESAs, producing comparable increases in hemoglobin. However, in advanced chronic kidney disease, HIF-PHD inhibitors can increase the risk of cardiovascular death, heart failure, and thrombotic events to a greater extent than that with ESAs, indicating that there is a compelling need for safer alternatives. Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of major cardiovascular events, and they increase hemoglobin, an effect that is related to an increase in erythropoietin and an expansion in red blood cell mass. SGLT2 inhibitors increase hemoglobin by ≈0.6-0.7 g/dL, resulting in the alleviation of anemia in many patients. The magnitude of this effect is comparable to that seen with low-to-medium doses of HIF-PHD inhibitors, and it is apparent even in advanced chronic kidney disease. Interestingly, HIF-PHD inhibitors act by interfering with the prolyl hydroxylases that degrade both HIF-1α and HIF-2α, thus enhancing both isoforms. However, HIF-2α is the physiological stimulus to the production of erythropoietin, and upregulation of HIF-1α may be an unnecessary ancillary property of HIF-PHD inhibitors, which may have adverse cardiac and vascular consequences. In contrast, SGLT2 inhibitors act to selectively increase HIF-2α, while downregulating HIF-1α, a distinctive profile that may contribute to their cardiorenal benefits. Intriguingly, for both HIF-PHD and SGLT2 inhibitors, the liver is likely to be an important site of increased erythropoietin production, recapitulating the fetal phenotype. These observations suggest that the use of SGLT2 inhibitors should be seriously evaluated as a therapeutic approach to treat renal anemia, yielding less cardiovascular risk than other therapeutic options.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"255-259"},"PeriodicalIF":4.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9524155","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}