American Journal of Nephrology最新文献

{"title":"Systemic Factors Contributing to Gender Differences in Living Kidney Donation: A Systematic Review and Meta-Synthesis Using the Social-Ecological Model Lens.","authors":"Katya Loban, Chloe Wong-Mersereau, Jewy Cates Ferrer, Lindsay Hales, Antoine Przybylak-Brouillard, Marcelo Cantarovich, Vivek B Kute, Anil K Bhalla, Rosemary Morgan, Shaifali Sandal","doi":"10.1159/000541890","DOIUrl":"10.1159/000541890","url":null,"abstract":"<p><strong>Introduction: </strong>The field of living kidney donation is profoundly gendered contributing to a predominance of women, mothers, and wives as living kidney donors (LKDs). Individual factors have traditionally been emphasized, and there is a limited appreciation of relational, community, and sociocultural influences in decision-making. We aimed to comprehensively capture existing evidence to examine the relative importance of these factors.</p><p><strong>Methods: </strong>This was a systematic review of existing literature that has explored the motivation of different genders to become LKDs. Of the 3,188 records screened, 16 studies from 13 counties were included. Data were synthesized thematically using the Social-Ecological Model lens.</p><p><strong>Results: </strong>At the individual level, themes related to intrinsic motivation; thoughtful deliberation; and attitudes, fears, and beliefs; however, evidence demonstrating differences between men and women was minimal. Greater variation between genders emerged along the relational (coercion from family/network, relationship with the intended recipient, self-sacrifice within the family unit, and stability/acceptance within family); community (economic value and geographic proximity to recipient); and sociocultural (gendered societal roles, social norms and beliefs, social privilege, and legislation and policy) dimensions. The relative importance of each factor varied by context; cultural components were inferred in each study, and economic considerations seemed to transcend the gender divide.</p><p><strong>Conclusions: </strong>A complex interplay of factors at relational, community, and sociocultural levels influences gender roles, relations, and norms and manifests as gender disparities in living kidney donation. Our findings suggest that to address gender disparities in living donation, dismantling of deep-rooted systemic contributors to gender inequities is needed.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"94-110"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387300","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":"Impairment of Renal Function in Hermansky-Pudlak Syndrome.","authors":"Tadafumi Yokoyama, Kevin J O'Brien, Tesiya M Franklin, Ben Long G Zuo, Mei Xing G Zuo, Melissa A Merideth, Wendy J Introne, Bernadette R Gochuico","doi":"10.1159/000541835","DOIUrl":"10.1159/000541835","url":null,"abstract":"<p><strong>Introduction: </strong>Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder characterized by defective biogenesis of lysosome-related organelles. The genetic types of HPS are associated with a spectrum of multisystemic clinical manifestations. Phenotypic features of HPS type 1 (HPS-1) or HPS-4, which are associated with defects in biogenesis of lysosome-related organelles complex-3 (BLOC-3), are generally more severe than those of HPS-3, HPS-5, or HPS-6, which are associated with defects in BLOC-2. A paucity of information is available about renal impairment in HPS. The objective of this study is to expand the understanding of kidney disease in HPS.</p><p><strong>Methods: </strong>Medical records and clinical data of patients with HPS evaluated at the National Institutes of Health Clinical Center from 1995 to 2020 were retrospectively reviewed. For patients with more than one visit, the most recent renal function and urinalysis tests were analyzed. Estimated glomerular filtration rate (eGFR) was calculated using standard equations (i.e., Chronic Kidney Disease Epidemiology Collaboration, Modification of Diet in Renal Disease). Kidney tissue sections from 5 patients with HPS-1 and 1 patient with HPS-6 were examined.</p><p><strong>Results: </strong>Records from 205 adults and 52 children with HPS were reviewed. Calculated eGFR of adult patients with different HPS types differed significantly, and calculated eGFR of pediatric and adult patients with BLOC-3 disorders was significantly lower than that of patients with BLOC-2 disorders. Linear regression analysis showed that renal function progressively decreases with age in patients with BLOC-3 or BLOC-2 disorders, but the rate of decline was more rapid in patients with BLOC-3 disorders compared to patients with BLOC-2 disorders. In adult patients with HPS-1, glucosuria was found in 4%, proteinuria in 12%, hematuria in 15%, high levels of urinary β2MG in 24%, and elevated urinary albumin to creatinine ratios in 9%. Histological examination of kidney tissue showed accumulation of intracellular deposits of ceroid lipofuscin in proximal renal tubular epithelial cells in patients with HPS-1. There was no evidence of fibrosis, and glomeruli, distal renal tubular epithelial cells, and interstitial regions appeared histologically normal.</p><p><strong>Conclusion: </strong>Mild impairment of renal function is a feature of HPS. Kidneys of patients with HPS-1 contain proximal renal tubular intracellular deposits and no histologic evidence of fibrosis. Consistent with other manifestations of HPS, the phenotype of renal impairment is relatively more pronounced in patients with BLOC-3 disorders than in patients with BLOC-2 disorders. Strategies to avoid nephrotoxicity or renal tubular injury and to protect renal function should be considered for patients with HPS irrespective of age.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"25-34"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11810587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387298","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 Interplay of Nonalcoholic Fatty Liver Disease and Chronic Kidney Disease: A Call for Integrated Management.","authors":"Carmine Zoccali, Francesca Mallamaci","doi":"10.1159/000541889","DOIUrl":"10.1159/000541889","url":null,"abstract":"","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"243-246"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581446","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 Impact of Primary Renal Diagnosis on Prognosis and the Varying Predictive Power of Albuminuria in the NURTuRE-CKD Study.","authors":"Thomas McDonnell, Philip A Kalra, Nicolas Vuilleumier, Paul Cockwell, David C Wheeler, Simon D S Fraser, Rosamonde E Banks, Maarten W Taal","doi":"10.1159/000541770","DOIUrl":"10.1159/000541770","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;The definition of CKD is broad, which neglects the heterogeneity of risk across primary renal diseases.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The National Unified Renal Translational Research Enterprise (NURTuRE)-CKD is an ongoing UK, prospective multicenter cohort study of 2,996 adults with an eGFR of 15-59 mL/min/1.73 m2 or eGFR ≥60 mL/min/1.73 m2 with a urine albumin-to-creatinine ratio (uACR) &gt;30 mg/mmol. Outcomes and predictive performance of eGFR and uACR were subcategorized by ERA-EDTA primary renal diagnosis (PRD) codes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;2,638 participants were included, with baseline median eGFR of 33.5 mL/min/1.73 m2 and uACR 29.8 mg/mmol. Over a median 49.2 months follow-up, 630 (23.9%) experienced kidney failure (KF), and 352 (13.3%) died before KF, the median eGFR slope was -1.97 mL/min/1.73 m2/year. There were significant differences in risk across the PRD, persisting after adjustment for age, sex, baseline eGFR, and modifiable risk factors (blood pressure, HbA1c, and renin-angiotensin-aldosterone system inhibitors). Diabetic kidney disease (DKD), glomerulonephritis, and familial/hereditary nephropathy were associated with the greatest risk, while tubulointerstitial disease and vasculitis carried a low risk of KF. eGFR had good predictive accuracy across all PRD. However, the addition of uACR showed variable benefit, depending on the PRD. The largest benefit was seen in vasculitis, renal vascular, and DKD groups, but uACR added no predictive value to the familial/hereditary group.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Significant differences in the risk of kidney-related outcomes occurred across the various primary renal diagnoses persisting after adjustment for age, sex, baseline eGFR, and modifiable risk factors. Albuminuria's discriminatory ability as a biomarker of progression varies by diagnosis. CKD care should, therefore, take a personalized approach that always considers the primary renal diagnosis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;The definition of CKD is broad, which neglects the heterogeneity of risk across primary renal diseases.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The National Unified Renal Translational Research Enterprise (NURTuRE)-CKD is an ongoing UK, prospective multicenter cohort study of 2,996 adults with an eGFR of 15-59 mL/min/1.73 m2 or eGFR ≥60 mL/min/1.73 m2 with a urine albumin-to-creatinine ratio (uACR) &gt;30 mg/mmol. Outcomes and predictive performance of eGFR and uACR were subcategorized by ERA-EDTA primary renal diagnosis (PRD) codes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;2,638 participants were included, with baseline median eGFR of 33.5 mL/min/1.73 m2 and uACR 29.8 mg/mmol. Over a median 49.2 months follow-up, 630 (23.9%) experienced kidney failure (KF), and 352 (13.3%) died before KF, the median eGFR slope was -1.97 mL/min/1.73 m2/year. There were significant differences in risk across the PRD, persisting after adjustment for age, sex, baseline eGFR, and modifiable ris","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-12"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11812588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379915","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":"Mineralocorticoid Receptor Antagonist Combined with SGLT2 Inhibitor versus SGLT2 Inhibitor Alone in Chronic Kidney Disease: A Meta-Analysis of Randomized Trials.","authors":"João Pedro Ferreira, Ana Cristina Oliveira, Francisco Vasques-Novoa, Ana Rita Leite, Luís Mendonça, Faiez Zannad, Javed Butler, Adelino Leite-Moreira, Francisca Saraiva, João Sérgio Neves","doi":"10.1159/000541686","DOIUrl":"10.1159/000541686","url":null,"abstract":"<p><strong>Introduction: </strong>Sodium glucose co-transporter 2 inhibitors (SGLT2i) and mineralocorticoid receptor antagonists (MRAs) reduce the progression of kidney disease. Whether the combination of these agents provides additional benefits compared to SGLT2i alone is worth exploring using data from randomized trials designed for this purpose. The aim of the study was to assess the randomized treatment effect of MRAs combined with SGLT2i versus SGLT2i alone on markers of kidney and cardiovascular health.</p><p><strong>Methods: </strong>Random-effects meta-analysis of randomized trials testing the combination of MRAs with SGLT2i versus SGLT2i alone on albuminuria, blood pressure, estimated glomerular filtration rate (eGFR), and serum potassium among patients with chronic kidney disease (CKD).</p><p><strong>Results: </strong>Four randomized trials were included with a total of 272 patients with CKD: eGFR varying between 30 and 60 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio (UACR) between 90 and 500 mg/g, with >60% having type 2 diabetes. Treatment with MRAs plus SGLT2i versus SGLT2i alone reduced UACR by -33.6% (-42.6 to -24.7%), p < 0.001, I2 = 0%. MRAs plus SGLT2i versus SGLT2i alone reduced systolic blood pressure by -6.1 mm Hg (-8.9 to -3.3) mm Hg, eGFR by -3.4 mm Hg (-5.2 to -1.6) mm Hg, and increased serum potassium by + 0.23 mmol/L (0.15-0.34) mmol/L; p < 0.001 for all, without significant heterogeneity between trials (I2 <25%).</p><p><strong>Conclusion: </strong>In this meta-analysis, MRAs plus SGLT2i provided greater reductions in albuminuria and blood pressure compared to SGLT2i alone. Larger randomized trials with longer follow-up should test whether MRA/SGLT2i combination therapies improve cardiovascular and renal outcomes compared to SGLT2i alone.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"236-242"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602576","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":"Kidney and Cardiovascular Outcomes in Older Population with Mildly to Moderately Decreased Kidney Function: A Nationwide Cohort Study.","authors":"Junseok Jeon, Dong Wook Shin, Sang Hyun Park, Jin-Hyung Jung, Kyungho Lee, Jung Eun Lee, Wooseong Huh, Kyungdo Han, Hye Ryoun Jang","doi":"10.1159/000541832","DOIUrl":"10.1159/000541832","url":null,"abstract":"<p><strong>Introduction: </strong>Although the prevalence of chronic kidney disease (CKD) is increasing in the aging population, the clinical relevance of the CKD definition (glomerular filtration rate [GFR] <60 mL/min/1.73 m2) in older populations remains debatable. We investigated the clinical outcomes in older populations with mildly to moderately decreased GFR (45-59 mL/min/1.73 m2, CKD stage 3A).</p><p><strong>Methods: </strong>A total of 7,789,242 participants aged ≥40 years with estimated GFR (eGFR) ≥45 mL/min/1.73 m2 in national health screening examination from 2012 to 2017 were included in this retrospective cohort study using the Korean National Health Insurance Service database. The main outcomes included kidney failure, cardiovascular disease (CVD), and all-cause death. Cox regression hazard models were used to estimate the hazard ratios.</p><p><strong>Results: </strong>The proportion of participants with eGFR 45-59 mL/min/1.73 m2 was 10.0% and 16.3% in the old (65-74 years) and very old (75≥ years) groups, respectively. Mildly to moderately decreased eGFR was associated with a higher risk of kidney failure, CVD, and all-cause death compared with eGFR 60-89 mL/min/1.73 m2 in the old and very old groups, regardless of proteinuria (adjusted hazard ratio [95% confidence interval] in the very old group without proteinuria: kidney failure 3.048 [2.495-3.722], CVD 1.103 [1.066-1.142], and all-cause death 1.172 [1.144-1.201]).</p><p><strong>Conclusion: </strong>Mildly to moderately decreased eGFR was associated with an increased risk of kidney failure, CVD, and all-cause death in the older population, regardless of proteinuria, suggesting the importance of appropriate monitoring and management in this population.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"123-135"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492883","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":"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":"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":"Plasma Transcriptome Profile Associated with Chronic Kidney Disease Progression.","authors":"Anvesha Srivastava, Mark Maienschein-Cline, Richard L Amdur, Katalin Susztak, Jeffrey Burnett Kopp, Haiming Cao, Divya Shankaranarayanan, Yoosif Abdalla, Ana Pabalan, Michael Gombert, Dominic Raj","doi":"10.1159/000542707","DOIUrl":"10.1159/000542707","url":null,"abstract":"<p><strong>Introduction: </strong>Understanding the molecular signals associated with the progression of kidney disease is vital for risk stratification and targeted treatment. Recent advances in RNA-sequencing technique have enabled us to characterize extracellular transcriptome profiles for precision diagnostics.</p><p><strong>Method: </strong>We evaluated the plasma mRNA profile of participants exhibiting slow (n = 119) and fast (n = 119) decline in estimated glomerular filtration rate (eGFR) among the Chronic Renal Insufficiency Cohort (CRIC) in a nested case control study. The two groups were matched for age, sex, race, baseline eGFR, proteinuria, and diabetes status. The next-generation sequencing data were analyzed using edgeR to identify differentially expressed genes (DEGs) and ingenuity pathway analysis was done to identify the associated pathways. We also compared the top plasma DEGs with gene expression in microdissected human chronic kidney disease (CKD) kidney.</p><p><strong>Results: </strong>We identified fragments from ∼28,000 annotated genes, of which 783 transcripts exhibited differential expression between slow and fast CKD progressors. Among 629 protein coding genes, 469 were overexpressed in slow progressors, while 157 showed increased expression in fast progressors. Expression of GLI2, CUX1, NOTCH1, and LRP1 transcripts were amplified in slow progressors. Pathway analysis linked these DEG to WNT/β-catenin signaling, IL-12 signaling and production in macrophages, Netrin-1 Signaling and Epithelial-Mesenchymal Transition pathways. Many of the plasma DEGs were also upregulated in microdissected human CKD kidney.</p><p><strong>Conclusion: </strong>Warranting further validation, circulating levels of aberrantly expressed transcripts hold potential to be used as biomarkers for fast CKD progression.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-13"},"PeriodicalIF":4.3,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852075","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}