American Journal of Nephrology最新文献

{"title":"Effects of Roxadustat on Thyroid Profiles in Patients and Animals with Chronic Kidney Disease.","authors":"Wangyang Li, Tao Cao, Guangluan Huang, Jianying Guo, Tangkun Zhu, Haofei Hu, Huiwei Huang, Xueting Liu, Liling Wu, Jia Chen, Dongli Qi, Tie Chen, Qijun Wan, Yuan Cheng","doi":"10.1159/000542699","DOIUrl":"10.1159/000542699","url":null,"abstract":"<p><strong>Introduction: </strong>Roxadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor used in renal anemia treatment, has been associated with thyroid hormone suppression. This study investigated the patterns of thyroid profile changes following roxadustat administration and their clinical implications.</p><p><strong>Methods: </strong>In this retrospective study (2019-2023) at Shenzhen Second People's Hospital, patients were categorized based on thyroid-stimulating hormone (TSH) reduction during follow-up (≥50% decrease vs. <50% decrease). Thyroid profiles, clinical symptoms, and laboratory indicators were analyzed. Quality of life was assessed using EQ-5D-3L and ThyPRO questionnaires. Complementary animal experiments were conducted to verify the effects of roxadustat on thyroid function.</p><p><strong>Results: </strong>A total of 118 patients were finally enrolled in our study. Among patients with initially normal thyroid function, 31 developed euthyroid sick syndrome post-roxadustat treatment. Treatment significantly decreased TT3, FT3, FT4, and TSH levels, with TSH showing marked reduction within the first 10 weeks. Contrastingly, animal models exhibited decreased T3 but increased TSH levels, regardless of renal status. Blood lipid levels decreased in all patients, particularly in those with substantial TSH reduction. Despite thyroid alterations, quality-of-life scores remained unchanged between roxadustat-treated and untreated patients, with no overt clinical symptoms in either humans or animals.</p><p><strong>Conclusion: </strong>While roxadustat induces significant thyroid hormone suppression in patients, these alterations rarely manifest as clinical symptoms. Euthyroid sick syndrome is the predominant thyroid dysfunction pattern observed. Regular thyroid function monitoring is recommended during roxadustat therapy, particularly during the initial treatment phase when TSH changes are most pronounced.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"351-365"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799130","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":"Associations of Causes of Chronic Kidney Disease with Disease Progression and Mortality: Insights from the Fukuoka Kidney Disease Registry Study.","authors":"Hiromasa Kitamura, Shigeru Tanaka, Hiroto Hiyamuta, Kazuhiko Tsuruya, Takanari Kitazono, Toshiaki Nakano","doi":"10.1159/000543201","DOIUrl":"10.1159/000543201","url":null,"abstract":"<p><strong>Introduction: </strong>The Kidney Disease: Improving Global Outcomes guidelines recognize the importance of causes of chronic kidney disease (CKD), glomerular filtration rate, and albuminuria as predictors of kidney outcome and prognosis. However, compared with biopsy-proven causes, there has been limited research regarding the relationship between clinically diagnosed causes of CKD and patient prognosis.</p><p><strong>Methods: </strong>We examined 3,119 patients with non-dialysis-dependent CKD who participated in the Fukuoka Kidney disease Registry Study, a multicenter prospective cohort study. Patients were divided into six groups: IgA nephropathy, chronic glomerulonephritis (non-biopsy-proven), diabetic nephropathy, hypertensive nephrosclerosis, chronic interstitial nephritis, and polycystic kidney disease. The primary outcomes included a composite kidney outcome, defined as a 1.5-fold increase in serum creatinine and/or the development of end-stage kidney disease, and all-cause mortality. The risks of these outcomes were estimated using a Fine-Gray proportional subdistribution hazards model. Patients with IgA nephropathy, the most prevalent primary glomerulonephritis, served as the reference group.</p><p><strong>Results: </strong>During the median follow-up period of 5 years, 1,221 patients developed the composite kidney outcome, and 346 patients died. Compared with IgA nephropathy, the multivariable-adjusted subdistribution hazard ratios (sHRs) for the composite kidney outcome were significantly higher in diabetic nephropathy (sHR 1.45) and polycystic kidney disease (sHR 2.07) groups, whereas the chronic interstitial nephritis group had a significantly lower risk (sHR 0.71). The risk of all-cause mortality was significantly higher in the hypertensive nephrosclerosis group (sHR 1.90).</p><p><strong>Conclusion: </strong>The causes of CKD were associated with risks of the composite kidney outcome and all-cause mortality, highlighting their clinical relevance in predicting prognosis. These findings suggest that different causes of CKD have distinct impacts on patient outcomes, emphasizing the importance of tailoring management strategies according to the underlying causes.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"366-376"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942486","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":"The Superiority of European Kidney Function Consortium Cystatin C-Based Formula for Risk Stratification of All-Cause and Cardiovascular Deaths in US Adults.","authors":"Zixiang Ye, Haixu Wang, Enmin Xie, Zeming Zhou, Kefei Dou","doi":"10.1159/000542912","DOIUrl":"10.1159/000542912","url":null,"abstract":"<p><strong>Introduction: </strong>We intended to compare the predictive value for all-cause and cardiovascular deaths between estimated glomerular filtration rate (eGFR) derived from the European Kidney Function Consortium (EKFC) cystatin C-based formula, the EKFC creatinine-based formula, and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) cystatin C- or creatinine-based formulas.</p><p><strong>Methods: </strong>Overall, 4,132 participants from the National Health and Nutrition Examination Survey between 1999 and 2002 were included, and death information was obtained through the National Death Index. To compare predictive accuracy between EKFC eGFRcys (EKFC cystatin C-based formula), CKD-EPI eGFRcys (CKD-EPI cystatin C-based formula), EKFC eGFRcr (EKFC creatinine-based formula), and CKD-EPI eGFRcr (CKD-EPI creatinine-based formula), we conducted time-dependent receiver operator characteristic (ROC) curves and reclassification analysis.</p><p><strong>Results: </strong>During a median follow-up of 17.4 years, a total of 1,987 all-cause and 530 cardiovascular deaths were confirmed. Restricted cubic splines analyses showed that reduced EKFC eGFRcys was linearly related to higher risks of all-cause and cardiovascular deaths (p for nonlinearity > 0.05). Time-dependent ROC curves suggested that EKFC eGFRcys exhibited higher predictive ability than CKD-EPI eGFRcys, EKFC eGFRcr, and CKD-EPI eGFRcr at 5-year and 10-year follow-ups. For 10-year all-cause deaths, EKFC eGFRcys yielded significant improvement over CKD-EPI eGFRcr (integrated discrimination improvement [IDI], 9.4%; net reclassification improvement [NRI], 39.7%). Similar improvement was observed in 10-year cardiovascular deaths when comparing EKFC eGFRcys to CKD-EPI eGFRcr (IDI, 6.7%; NRI, 45.1%).</p><p><strong>Conclusion: </strong>The EKFC eGFRcys outperformed CKD-EPI eGFRcys, EKFC eGFRcr, and CKD-EPI eGFRcr in predicting all-cause and cardiovascular deaths, providing the possibility to utilize EKFC eGFRcys in the stratification of death risk among the general US population.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"267-278"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998584","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":"Discovering Novel Loci of Chronic Kidney Disease via Principal Component Analysis-Based Multiple-Trait Genome-Wide Association Study.","authors":"Gwo-Tsann Chuang, Chia-Ni Hsiung, Tony Pan-Hou Che, Yi-Cheng Chang","doi":"10.1159/000541982","DOIUrl":"10.1159/000541982","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic kidney diseases (CKD) encompass a spectrum of complex pathophysiological processes. While numerous genome-wide association studies (GWASs) have focused on individual traits such as albuminuria, estimated glomerular filtration rate (eGFR), and eGFR change, there remains a paucity of genetic studies integrating these traits collectively for comprehensive evaluation.</p><p><strong>Methods: </strong>In this study, we performed individual GWASs for albuminuria, baseline eGFR, and eGFR slope utilizing data from non-diabetic individuals enrolled from the Taiwan Biobank (TWB). Subsequently, we employed principal component analysis to transform these three quantitative traits into principal components (PCs) and performed GWAS based on these principal components (PC-based GWAS).</p><p><strong>Results: </strong>The individual GWAS analyses of albuminuria, baseline eGFR, and eGFR slope identified 10, 13, and 210 candidate loci respectively, with 2, 3, and 99 of them representing previously reported loci. PC-based GWAS identified additional 20 novel candidate loci linked to CKD (p values ranging from 5.8 × 10-7 to 9.1 × 10-6). Notably, 4 of these 20 single nucleotide polymorphisms (rs9332641, rs10737429, rs117231653, and rs73360624) exhibited significant associations with kidney expression quantitative trait loci.</p><p><strong>Conclusion: </strong>To our knowledge, this study represents the first PC-based GWAS integrating albuminuria, baseline eGFR, and eGFR slope. Our approach found 20 novel candidate loci suggestively associated with CKD, underscoring the value of integrating multiple kidney traits in unraveling the pathophysiology of this complex disorder.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"198-210"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11975323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455856","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":"A Risk Prediction Model for New-Onset Chronic Kidney Disease in the Elderly.","authors":"Wei Luo, Li Lei, Jinchuan Lai, Yumiao Liu, Hongbin Liang, Shaohua Yan, Xiong Gao, Hongshan Chen, Wenqing Nai, Xinlu Zhang, Qiuxia Zhang, Min Xiao, Jiancheng Xiu","doi":"10.1159/000541510","DOIUrl":"10.1159/000541510","url":null,"abstract":"<p><strong>Introduction: </strong>Worsening renal function poses a significant health risk to elderly individuals. This study aimed to construct a simple risk prediction model for new-onset chronic kidney disease (CKD) among elderly populations.</p><p><strong>Methods: </strong>In this retrospective cohort study, 5,416 elderly residents (aged ≥65 years) who underwent physical examinations as part of the National Basic Public Health Service project at least twice between January 2017 and July 2021 were included. The endpoint was new-onset CKD, defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 during the follow-up period. Predictors of new-onset CKD were selected using multivariable Cox regression and a stepwise approach. A risk prediction model based on the selected predictors was constructed and evaluated using the concordance index (C-index) and area under curve (AUC). External validation was conducted to verify the model's performance.</p><p><strong>Results: </strong>During the median follow-up period of 2.3 years, the incident of new-onset CKD was 20.1% (n = 1,088). Age, female gender, diabetes, elevated triglyceride levels, and baseline eGFR were selected as predictors. The model demonstrated good predictive performance across the cohort, with a C-index of 0.802. The AUCs for 2-year, 3-year, and 4-year predictions were 0.831, 0.829, and 0.839, respectively. External validation confirmed the model's efficacy, with a 2-year AUC of 0.735.</p><p><strong>Conclusion: </strong>This study developed a simple yet effective risk prediction model for new-onset CKD among elderly populations. The model facilitates prompt identification of elderly individuals at risk of renal function decline in primary care, enabling timely interventions.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"58-69"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142306853","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":"Long-Term Efficacy and Safety of Upacicalcet in Japanese Hemodialysis Patients with Secondary Hyperparathyroidism: Open-Label 52-Week Study.","authors":"Takayuki Hamano, Fumihiko Koiwa, Yoshitaka Isaka, Keitaro Yokoyama, Masafumi Fukagawa, Yosuke Inagaki, Yukihisa S Watanabe, Daisuke Honda, Tadao Akizawa","doi":"10.1159/000541493","DOIUrl":"10.1159/000541493","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Upacicalcet is a novel injectable calcimimetic. This phase 3 multicenter open-label study aimed to assess the long-term efficacy and safety of upacicalcet in hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Japanese HD patients with serum intact parathyroid hormone (iPTH) levels &gt;240 pg/mL and corrected calcium (cCa) levels ≥8.4 mg/dL were enrolled. Upacicalcet with a dose range of 25-300 µg was administered after each dialysis for 52 weeks. The main efficacy endpoint was the percentage of patients achieving the target iPTH level (60-240 pg/mL).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 157 patients were enrolled, of whom 138 completed the study. Overall, 94.2% of patients achieved the target serum iPTH level at week 52. Neither symptomatic hypocalcemia nor cCa level &lt;7.5 mg/dL occurred despite the negligible increase of concomitant vitamin D receptor activators and calcium carbonate. Upacicalcet improved the control of serum phosphate (P) and calcium levels regardless of baseline PTH levels and decreased intact fibroblast growth factor-23 levels. The largest parathyroid glands shrank, irrespective of their baseline volume or prior calcimimetic usage. Upacicalcet was well tolerated, with no adverse events requiring dose reduction.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This is the first study to show that a calcimimetic improves serum P and cCa control without inducing severe hypocalcemia in patients with iPTH levels ≤300 pg/mL. Upacicalcet is efficacious in HD patients with mild-to-severe SHPT, with few safety concerns.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Upacicalcet is a novel injectable calcimimetic. This phase 3 multicenter open-label study aimed to assess the long-term efficacy and safety of upacicalcet in hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Japanese HD patients with serum intact parathyroid hormone (iPTH) levels &gt;240 pg/mL and corrected calcium (cCa) levels ≥8.4 mg/dL were enrolled. Upacicalcet with a dose range of 25-300 µg was administered after each dialysis for 52 weeks. The main efficacy endpoint was the percentage of patients achieving the target iPTH level (60-240 pg/mL).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 157 patients were enrolled, of whom 138 completed the study. Overall, 94.2% of patients achieved the target serum iPTH level at week 52. Neither symptomatic hypocalcemia nor cCa level &lt;7.5 mg/dL occurred despite the negligible increase of concomitant vitamin D receptor activators and calcium carbonate. Upacicalcet improved the control of serum phosphate (P) and calcium levels regardless of baseline PTH levels and decreased intact fibroblast growth factor-23 levels. The largest parathyroid glands shrank, irrespective of their baseline volume or prior calcimimetic usage. Upacicalcet was well tolerated, with no adverse events requiring dose reduction.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"70-84"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11812589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279055","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":"Performance of New Race-Free eGFR Equations for Predicting Complications in Chronic Kidney Disease: From the KNOW-CKD Study.","authors":"Jaehee Koh, Jihyun Yang, Kyu-Beck Lee, Jayoun Kim, Jong Cheol Jeong, Yaeni Kim, Tae-Hyun Yoo, Kook-Hwan Oh, Young Youl Hyun","doi":"10.1159/000543324","DOIUrl":"10.1159/000543324","url":null,"abstract":"<p><strong>Introduction: </strong>The National Kidney Foundation (NKF) and the American Society of Nephrology (ASN) developed new race-free eGFR equations and recommended using these new equations in 2021. However, clinical implication of these new equations is not determined in Korean adults. Thus, this study aimed to evaluate performances of these new race-free eGFR equations in predicting complications in Korean chronic kidney disease (CKD) patients.</p><p><strong>Methods: </strong>This study analyzed 1,727 participants from the KNOW-CKD cohort. We selected anemia, hyperkalemia, acidosis, hyperphosphatemia, and hyperparathyroidism as five complications of CKD. We determined cross-sectional associations between complications and four eGFR equations. These eGFRs were calculated from 2009 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation (2009 eGFRCr), 2012 CKD-EPI Creatinine-Cystatin C equation (2012 eGFRCrCys), 2021 CKD-EPI Creatinine equation (2021 eGFRCr), and 2021 CKD-EPI Creatinine-Cystatin C equation (2021 eGFRCrCys).</p><p><strong>Results: </strong>All associations between complications as continuous variables and eGFR by four equations were similar. All associations between complications as dichotomous variable and eGFR values form four equations were similar. For example, C-statistics (95% confidence interval) of the logistic model for anemia and eGFRs were 0.826 (0.806-0.845), 0.827 (0.806-0.846), 0.838 (0.819-0.857), and 0.839 (0.820-0.858) for 2009 eGFRCr, 2012 eGFRCrCys, 2021 eGFRCr, and 2021 eGFRCrCys, respectively. In addition, cross-validated areas under the curve for ROC analysis after predictive modeling for all complications were not significant different according to different eGFR equations.</p><p><strong>Conclusion: </strong>New race-free eGFR equations showed similar performances to existing equations for predicting complications in Korean patients with CKD.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"329-336"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12169797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920348","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":"Erratum.","authors":"","doi":"10.1159/000543485","DOIUrl":"10.1159/000543485","url":null,"abstract":"","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"389-390"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412847","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":"Does Correction of Secondary Hyperparathyroidism with Extended-Release Calcifediol Provide Renoprotection?","authors":"Martin H de Borst","doi":"10.1159/000541614","DOIUrl":"https://doi.org/10.1159/000541614","url":null,"abstract":"","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-3"},"PeriodicalIF":4.3,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492882","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":"Sustained Reduction of Elevated Intact Parathyroid Hormone Concentrations with Extended-Release Calcifediol Slows Chronic Kidney Disease Progression in Secondary Hyperparathyroidism Patients.","authors":"Charles W Bishop, Akhtar Ashfaq, Stephen A Strugnell, John Choe, Nilay Patel, Keith C Norris, Stuart M Sprague","doi":"10.1159/000541138","DOIUrl":"10.1159/000541138","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic kidney disease (CKD) drives onerous human and healthcare costs, underscoring an urgent need to avert disease progression. Secondary hyperparathyroidism (SHPT) develops as CKD advances, and persistently elevated parathyroid hormone (PTH) may be nephrotoxic and associated with earlier dialysis onset. This study examines, for the first time, the hypothesis that sustained reduction of elevated intact PTH (iPTH) with extended-release calcifediol (ERC) reduces the nephrotoxic impact of SHPT and forestalls renal decline.</p><p><strong>Methods: </strong>Changes in estimated glomerular filtration rate (eGFR) were analyzed post hoc in 126 adults with SHPT, stage 3-4 CKD, and low serum 25-hydroxyvitamin D (25D) treated for 1 year with ERC in pivotal trials. ERC was administered at 30 μg/day increasing, as needed, to 60 μg/day to achieve ≥30% reductions in iPTH. Calcium, phosphorus, 25D, 1,25-dihydroxyvitamin D (1,25D), iPTH, eGFR, fibroblast growth factor-23 (FGF23), bone turnover markers (BTMs), and urine albumin-to-creatinine ratio (uACR) were measured at baseline and regular intervals. Participants were categorized by achievement (or not) of sustained ≥30% iPTH reductions over the last 2 quarters of treatment to evaluate differences in eGFR decline.</p><p><strong>Results: </strong>For all participants, 25D increased 58.5 ± 2.3 (SE) ng/mL (p &lt; 0.001) by the end of treatment (EOT), 1,25D increased 10.1 ± 1.8 pg/mL (p &lt; 0.001), iPTH decreased from 143.8 ± 5.8 pg/mL to 108.8 ± 7.2 (p &lt; 0.001), BTMs improved (p &lt; 0.01), and eGFR declined 2.2 ± 0.5 mL/min/1.73 m2 (p &lt; 0.001). The rate of eGFR decline was &gt;5-fold higher (p = 0.014) in participants who did not achieve sustained iPTH reductions of ≥30% (3.2 ± 0.7; 12.7 ± 2.2%) than in those who did (0.6 ± 0.8; 2.9 ± 2.4%). It was highest in the 30 participants who did not exhibit an iPTH lowering response in both of the last 2 quarters of treatment (5.4 ± 0.9; 20.9 ± 3.4%). Duration of iPTH reduction had no impact on safety parameters. Degree of iPTH reduction at EOT was also associated with slower CKD progression.</p><p><strong>Conclusion: </strong>Sustained reduction of elevated iPTH with ERC treatment was associated with slower rates of eGFR decline in patients with SHPT and stage 3-4 CKD without raising safety concerns. A prospective trial is warranted to confirm this finding.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-10"},"PeriodicalIF":4.3,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078858","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}