American Journal of Nephrology最新文献

{"title":"Non-Alcoholic Fatty Liver Disease and Its Association with Kidney and Cardiovascular Outcomes in Moderate to Advanced Chronic Kidney Disease.","authors":"Cheol Ho Park, Hyunsun Lim, Youn Nam Kim, Jae Young Kim, Hyung Woo Kim, Tae Ik Chang, Seung Hyeok Han","doi":"10.1159/000541803","DOIUrl":"10.1159/000541803","url":null,"abstract":"<p><strong>Introduction: </strong>Non-alcoholic fatty liver disease (NAFLD) has emerged as a potential indicator for cardio-metabolic risk. However, clinical implications of NAFLD in patients with chronic kidney disease (CKD) are still elusive. We investigated to explore the association between NAFLD and adverse clinical outcomes among patients with CKD.</p><p><strong>Methods: </strong>In this national population-based retrospective cohort study, we analyzed 816,857 individuals who underwent National Health Insurance Service health examinations and had an estimated glomerular filtration rate of 15-59 mL/min/1.73 m2. The main predictor was the fatty liver index (FLI), a surrogate marker for NAFLD. The primary outcome was a composite cardiovascular or kidney events, which were examined combined or separately.</p><p><strong>Results: </strong>During a median follow-up of 7.7 (IQR, 6.4-9.6) years, the composite outcome events occurred in 74,266 (9.1%) individuals. Among these, there were 55,525 (6.8%) cardiovascular events and 22,961 (2.8%) kidney events, respectively. Compared to FLI of <30, the hazard ratio (HRs; 95% confidence intervals [CIs]) for the composite outcome were 1.16 (1.14-1.18) and 1.30 (1.26-1.33) for the FLIs of 30-59 and ≥60, respectively. The corresponding HRs for cardiovascular events were 1.21 (95% CI, 1.18-1.23) and 1.36 (95% CI, 1.31-1.40), respectively. Furthermore, FLIs of 30-59 and ≥60 were associated with an 11% (HR, 1.11; 95% CI, 1.07-1.15) and 24% (HR, 1.24; 95% CI, 1.17-1.30) increased risk of kidney events, respectively.</p><p><strong>Conclusions: </strong>NAFLD was associated with higher risk of adverse clinical outcomes in individuals with CKD. These findings suggest that NAFLD, as assessed by the FLI, can serve as a predictor of cardiovascular and kidney events in CKD population.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"13-24"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379914","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":"Sex Differences in the Risk of Bladder Cancer among Kidney Transplant Recipients and Patients with Kidney Failure Receiving Hemodialysis: A Nationwide Cohort Study.","authors":"Hoon Yu, Sung Jin Kim, Yoonjong Bae, Mina Kim, Chan-Young Jung","doi":"10.1159/000543298","DOIUrl":"10.1159/000543298","url":null,"abstract":"<p><strong>Introduction: </strong>Although both patients with kidney failure (KF) receiving hemodialysis (HD) and kidney transplantation (KT) recipients (KTRs) have a high risk of bladder cancer, how this risk changes in the transition from dialysis to KT is unknown. In this study, we aimed to investigate the risk of bladder cancer in KTRs and patients on HD.</p><p><strong>Methods: </strong>This was a nationwide longitudinal cohort study of 66,547 participants from the National Health Insurance Service cohort who started HD for patients with KF or who received KT from 2002 to 2020. The primary outcome was the diagnosis of bladder cancer, which was defined as the composite of diagnostic codes and either hospitalization or ≥2 outpatient visits for bladder cancer.</p><p><strong>Results: </strong>During mean follow-ups of 4.2 and 7.9 years in the HD and KT groups, respectively, the incidence rates of bladder cancer were 1.1/1,000 and 0.3/1,000 person-years, respectively. In the time-dependent multivariable Cox models, compared to patients on HD, the adjusted hazard ratio (aHR) for bladder cancer among KTRs was 0.36 (95% confidence interval [CI], 0.21-0.60; p < 0.001). Among men, this aHR was 0.29 (95% CI, 0.15-0.55; p < 0.001); however, no statistically significant association between the kidney replacement therapy modality and the risk of bladder cancer was observed among women. Landmark analysis performed to avoid immortal time bias by redefining time zero as a specific landmark time (2 and 5 years after HD initiation or KT) revealed similar results.</p><p><strong>Conclusion: </strong>The risk of bladder cancer was significantly lower among KTRs than that among patients receiving HD, particularly among men.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"258-266"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942609","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":"Supplement-Induced Acute Kidney Injury Reproduced in Kidney Organoids.","authors":"Hiroyuki Nakanoh, Kenji Tsuji, Kazuhiko Fukushima, Soichiro Haraguchi, Shinji Kitamura, Jun Wada, Kenji Tsuji","doi":"10.1159/000544795","DOIUrl":"10.1159/000544795","url":null,"abstract":"<p><strong>Introduction: </strong>Acute kidney injury associated with the consumption of Beni-koji CholesteHelp supplements, which contain red yeast rice (Beni-Koji), has become a significant public health concern in Japan. While renal biopsy findings from several case reports have suggested tubular damage, no definitive causal relationship has been established, and the underlying mechanisms of kidney injury remain poorly understood. The complexity of identifying toxic substances in supplements containing various bioactive compounds makes conventional investigative approaches both time-consuming and challenging. This highlights an urgent need to establish a reliable platform for assessing organ-specific toxicity in such supplements. In this study, we utilized a kidney organoid model derived from adult rat kidney stem cells (KS cells) to assess the potential tubular toxicity of these supplements.</p><p><strong>Methods: </strong>KS cell clusters were cultured in three-dimensional system supplemented with growth factors to promote kidney organoids. The organoids were subsequently exposed to Beni-koji CholesteHelp supplements or cisplatin, followed by histological and molecular analyses to evaluate structural impacts.</p><p><strong>Results: </strong>Established organoids had the kidney-like structures including tubular-like structures and glomerulus-like structures at the tips of multiple tubules. Treatment with Beni-koji CholesteHelp supplements induced significant tubular damage in the organoids, characterized by epithelial cell thinning, structural disruption, and increase in cleaved-caspase 3-positive apoptotic tubular cells, similar to the organoids treated with cisplatin.</p><p><strong>Conclusion: </strong>These findings provide the first evidence suggesting that certain toxicants in specific batches of Beni-koji CholesteHelp supplements cause direct renal tubular injury. This KS cell-based organoid system represents a cost-effective, reproducible, and technically simple platform for nephrotoxicity screening.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"520-528"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12342697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466508","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":"Fibroblast Growth Factor 23, Endogenous Erythropoietin, Erythropoiesis-Stimulating Agents, and Erythropoietin Resistance in Hemodialysis Patients.","authors":"Naoto Hamano, Hirotaka Komaba, Hisae Tanaka, Hiroo Takahashi, Yuichiro Takahashi, Toru Hyodo, Miho Hida, Takao Suga, Takehiko Wada, Takatoshi Kakuta, Masafumi Fukagawa, Hirotaka Komaba","doi":"10.1159/000543506","DOIUrl":"10.1159/000543506","url":null,"abstract":"<p><strong>Introduction: </strong>Recent experimental studies have reported that fibroblast growth factor 23 (FGF23) inhibits erythropoiesis by suppressing erythropoietin (EPO) production and downregulating the EPO receptor. Conversely, either endogenous or exogenous EPO has been shown to stimulate FGF23 production. However, little is known about the relationships between FGF23, erythropoiesis-stimulating agent (ESA) treatment, ESA resistance, and endogenous EPO in hemodialysis patients.</p><p><strong>Methods: </strong>We analyzed cross-sectional data from a cohort of 654 maintenance hemodialysis patients. We examined the associations of intact or C-terminal FGF23 with ESA treatment, ESA resistance index (ERI), hemoglobin, C-reactive protein, and endogenous EPO levels using linear regression models. EPO was measured only in patients not receiving ESAs.</p><p><strong>Results: </strong>A total of 458 patients (70%) were treated with ESAs. The median EPO concentration in non-ESA users was 7.8 (interquartile range, 5.3-14.4) mIU/mL. The median levels of intact and C-terminal FGF23 were 1,598 (interquartile range, 548-4,586) pg/mL and 38.7 (interquartile range, 14.0-127.6) pmol/L, respectively, in non-ESA users and 1,955 (interquartile range, 573-5,264) pg/mL and 41.4 (interquartile range, 13.9-116.8) pmol/L, respectively, in ESA users. After adjustment for potential confounders, higher ESA dose was associated with higher FGF23 levels measured by both intact and C-terminal assays. Higher C-terminal FGF23 was also associated with higher ERI, lower hemoglobin, and higher endogenous EPO, but no such associations were observed for intact FGF23 levels.</p><p><strong>Conclusions: </strong>Both intact and C-terminal FGF23 showed similar associations with ESA dose, but they showed different patterns of association with other parameters related to anemia. Further research is needed to elucidate the mechanisms underlying these different associations.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"403-411"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466494","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 Renin-Angiotensin-Aldosterone System Inhibition on Advanced Chronic Kidney Disease Progression: A Retrospective Observational Study.","authors":"Lukas Westermann, Janis M Nolde, Johannes Wiegel, Georg Büchler, Frederic Arnold, Thomas Welte, Frederic Arnold","doi":"10.1159/000543487","DOIUrl":"10.1159/000543487","url":null,"abstract":"<p><strong>Introduction: </strong>Maintaining renin-angiotensin-aldosterone system inhibition (RAASi) in advanced chronic kidney disease (CKD) to delay CKD progression is still controversial. This is due to potential side effects associated with RAASi, such as a decline in glomerular filtration rate (GFR) and hyperkalemia. This study aimed to examine the effect of RAASi on progression of advanced CKD to kidney failure (estimated glomerular filtration rate [eGFR] <15 mL/min/1.73 m2, CKD stage 5) in a real-life outpatient cohort.</p><p><strong>Methods: </strong>This single-center retrospective observational study presents data from 954 individuals with advanced CKD (eGFR 15-30 mL/min/1.73 m2), comparing 806 RAASi with 511 control intervals over a median follow-up period of 19 months. The endpoint was defined as time to manifestation of kidney failure. Univariate and multivariate time-to-event analyses were performed to assess effects of RAASi on endpoint probabilities.</p><p><strong>Results: </strong>Univariate time-to-event analysis did not show a significant difference in the median time to kidney failure between RAASi and control intervals (7.6 vs. 7.0 years, p = 0.74). Covariate-adjusted multivariate regression models also demonstrated no association between RAASi treatment and progression to kidney failure in patients with advanced CKD (hazard ratio 0.92 [95% CI: 0.67-1.23], p = 0.63).</p><p><strong>Conclusion: </strong>RAASi has no significant impact on the time to kidney failure in patients with advanced CKD. Hence, this study supports maintenance of RAASi in advanced CKD, if used for extrarenal indications such as cardiovascular protection.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"500-509"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514390","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":"Relationship between Podocyte Injury and Renal Outcomes in Patients with Acute Kidney Injury: A Report from a Retrospective Study in China.","authors":"Hongqi Ren, Shun Wu, Mengling Guo, Yudan Wang, Yilun Zhou, Liyuan Zhang, Yun Zhou, Yuanyuan Xing, Dong Sun, Xueqing Hu, Zhenmin Ruan, John Cijiang He, Hongqi Ren","doi":"10.1159/000543789","DOIUrl":"10.1159/000543789","url":null,"abstract":"<p><strong>Introduction: </strong>Podocyte injury has been proven to be a major cause for poor renal outcomes after acute kidney injury (AKI). However, clinical trial data are still limited. This study aimed to explore the clinical correlations between podocyte injury and renal outcomes in hospitalized AKI patients.</p><p><strong>Method: </strong>This retrospective study analyzed data on 52 AKI patients who were histologically diagnosed with acute tubular necrosis or acute interstitial nephritis from six centers throughout China between January 2012 and June 2023. Patients were classified into two groups based on the degree of foot process fusion: ≤50% (mild podocyte injury group) and >50% (severe podocyte injury group). The outcomes were post-AKI new-onset proteinuria and incident CKD.</p><p><strong>Results: </strong>Among 52 AKI patients (14 male; median age, 49 [30, 56] years), 28 (53.8%) had mild podocyte injury; 24 (46.2%) had severe podocyte injury. After 12-month follow-up, 16 (57.1%) had post-AKI new-onset proteinuria, and 5 (17.9%) had post-AKI incident CKD in mild podocyte injury group. Twenty (83.3%) had post-AKI new-onset proteinuria, and 14 (58.3%) had post-AKI incident CKD in severe podocyte injury group. Patients with more severe foot process fusion exhibited significantly higher incidences of post-AKI new-onset proteinuria (83.3% vs. 57.1%, p = 0.041) and incident CKD (58.3% vs. 17.9%, p = 0.003) at 12 months following AKI. The degree of foot process fusion (95% CI 1.013∼3.88, p = 0.048) and proteinuria at 3 months (95% CI 1.309∼5.443, p = 0.015) were identified as independent risk factors for post-AKI new-onset proteinuria at 12 months. The degree of foot process fusion (95% CI 1.026∼14.196, p = 0.048), and the presence of partial renal pathological features, including tubular atrophy (95% CI 1.012∼5.958, p = 0.030), interstitial inflammation (95% CI 1.005∼6.846, p = 0.039), interstitial fibrosis (95% CI 1.110∼6.075, p = 0.043) were independent risk factors for post-AKI incident CKD at 12 months. Kaplan-Meier analysis shows severe podocyte injury group had worst renal survival, including post-AKI new-onset proteinuria (p = 0.0066) and incident CKD (p = 0.0455).</p><p><strong>Conclusion: </strong>The degree of podocyte injury is an independent risk factor for post-AKI new-onset proteinuria and incident CKD in patients, and patients with more severe podocyte injury exhibit a higher incidence of post-AKI new-onset proteinuria and incident CKD.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"595-604"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051002","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":"Comprehensive Evaluation of the Cardiovascular Protective Effects of Sodium-Glucose Cotransporter 2 Inhibitors in Patients with Advanced Chronic Kidney Disease: A Real-World Evidence.","authors":"Chih-Chung Shiao, Ching-Wen Chiu, Yu-Ming Chang, Ming-Che Liu, Phung-Anh Nguyen, Thanh-Phuc Phan, Chia-Te Liao, Chih-Wei Huang, Christianus Heru Setiawan, Hui-Hsin Cheng, Min-Huei Hsu, Jason C Hsu","doi":"10.1159/000542132","DOIUrl":"10.1159/000542132","url":null,"abstract":"<p><strong>Introduction: </strong>Diabetes, kidney disease, and cardiovascular disease have complex interactions and coexistences that significantly worsen a patient's overall health. Previous research results have shown that SGLT2i hypoglycemic drugs can not only effectively control blood sugar in diabetic patients but also protect the kidneys and heart. This study further focuses on diabetic patients with kidney disease to explore the effectiveness of using SGLT2i hypoglycemic drugs in avoiding heart-related complications or death.</p><p><strong>Methods: </strong>This is a multicenter retrospective cohort study using the Taipei Medical University Clinical Research Database (TMUCRD) as the data source. This study selected patients who suffered from both type 2 diabetes and chronic kidney disease from 1 January 2008 to 31 December 2020, as the research team. Integrated or separate 4-point major adverse cardiovascular events (4P-MACE) and mortality were the outcomes of this study. The Kaplan-Meier curves method and Cox proportional hazard regression analysis were used to explore the association between each influencing factor and the outcome.</p><p><strong>Results: </strong>A total of 5,005 patients with type 2 diabetes and CKD were included in this study, of which 524 patients were stably treated with SGLT2i, 3,952 patients were treated with DPP4i, and 529 patients were treated with TZD. The results showed that the SGLT2i user group had a significantly lower risk of 4P-MACE compared with the SGLT2i nonuser group (hazard ratio [HR]: 0.68, 95% CI [0.49, 0.95], p = 0.024). The SGLT2i group had a significantly lower risk of cardiovascular mortality compared with the DPP4i and TZD groups (HR: 0.37, 95% CI [0.21, 0.65], p < 0.001; HR: 0.42, 95% CI [0.20, 0.90], p = 0.025).</p><p><strong>Conclusion: </strong>This study found that for patients with both diabetes and kidney disease, SGLT2i is a better option than other oral hypoglycemic medications because it can significantly avoid the occurrence of heart-related complications. The results of this study can be used as a reference for clinical medication selection practice.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"211-221"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455855","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":"Association between Serum Iron Store Biomarkers and All-Cause Mortality in Japanese Patients Undergoing Hemodialysis: A Nationwide Cohort Study.","authors":"Hiroki Nishiwaki, Takahiro Imaizumi, Takeshi Hasegawa, Takaaki Kosugi, Yukio Maruyama, Kazuhiko Tsuruya, Yasuhiko Ito, Hirokazu Honda, Masanori Abe, Norio Hanafusa, Takahiro Kuragano","doi":"10.1159/000543888","DOIUrl":"10.1159/000543888","url":null,"abstract":"<p><strong>Introduction: </strong>We evaluated the association between iron-related biomarkers - key indicators of iron metabolism and inflammation, and crucial in the management of anemia in patients undergoing hemodialysis - and all-cause mortality. This study aimed to clarify the nuanced relationship between these biomarkers and mortality outcomes, addressing the limitations of traditional cutoff-based analyses.</p><p><strong>Methods: </strong>We conducted a cohort analysis of patients undergoing dialysis across Japan using data from the Japan Renal Database collected between 2019 and 2020. Patients who had been on dialysis for at least 3 months by the end of 2019 were considered eligible. The associations between iron-related biomarkers and all-cause within 1 year were analyzed using Cox proportional hazards models. The relationship between each biomarker and outcome was illustrated using restricted cubic spline curves, while the combined association of serum ferritin and transferrin saturation (TSAT) with mortality was shown using contour plots.</p><p><strong>Results: </strong>A total of 215,927 patients were included in the analysis. During the follow-up period, 17,803 (8.24%) deaths were recorded. Contour plots demonstrated increased mortality risk in areas with low ferritin and TSAT levels. Additionally, even in regions with high TSAT levels, there was a trend toward increased mortality risk with increasing ferritin levels. Conversely, in areas with low ferritin levels, there was a trend toward a decreased risk of death with increasing TSAT.</p><p><strong>Conclusions: </strong>Our findings highlight the complex interplay between serum ferritin and TSAT levels, emphasizing the limitations of relying on single cutoff values for clinical decision-making. The study underscores the need for individualized approaches to iron management in patients undergoing hemodialysis.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"318-328"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078432","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 New Model of Chronic Kidney Disease, Metabolic Derangements, and Heart Failure with Preserved Ejection Fraction in Aging Swine.","authors":"Alejandro R Chade, Darla L Tharp, Rhys Sitz, Elizabeth A McCarthy, Kumar Shivam, Sara Kazeminia, Alfonso Eirin","doi":"10.1159/000543327","DOIUrl":"10.1159/000543327","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic kidney disease (CKD) and heart failure with preserved ejection fraction (HFpEF) are more prevalent in the elderly. There is a lack of large animal models that allow the study of the impact of age on CKD and HFpEF in a translational fashion. This manuscript reports the first large preclinical model of CKD-HFpEF and metabolic derangements in naturally aged swine.</p><p><strong>Methods: </strong>CKD-HFpEF was induced in naturally aged (6-9 years old) and young (3 months old) pigs, followed for 14 weeks, and compared to normal young and old controls (n = 5/group). Renal and cardiac hemodynamics were quantified in vivo by multidetector-CT, echocardiography, and pressure-volume relationship studies. Renal and cardiac microvascular (MV) architecture (3D-micro-CT) and morphometric analysis (staining) were investigated ex vivo.</p><p><strong>Results: </strong>Both young and old pigs developed CKD-HFpEF, but the renal, cardiac, and metabolic phenotype was accentuated in aging animals. Aging and CKD-HFpEF influenced fasting insulin levels and insulin resistance, glomerular filtration rate, cortical MV density, glomerulosclerosis, perivascular fibrosis, and tubular injury. Tubule-interstitial fibrosis and peritubular capillary density were influenced by aging, CKD-HFpEF, and their interaction (2-way ANOVA). Similarly, cardiac MV density, perivascular fibrosis, and myocardial remodeling were influenced by aging and CKD-HFpEF, and E/A by their interaction. Notably, renal and cardiac MV density correlated with renal and cardiac functional and structural changes.</p><p><strong>Conclusion: </strong>Our study establishes the first large animal model of aging CKD-HFpEF, allowing the investigation of age as a biological variable in cardiorenal and metabolic diseases. This new platform could foster new age-related research toward developing therapeutic interventions in CKD-HFpEF.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"337-350"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920347","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":"Assessing Predictors of Acute and Chronic Thrombotic Microangiopathy in Native and Allograft Biopsies.","authors":"Anam Tariq, Dominic Raj, Azka Tariq, Lois Arend, Mohamed G Atta","doi":"10.1159/000542025","DOIUrl":"10.1159/000542025","url":null,"abstract":"<p><strong>Introduction: </strong>Thrombotic microangiopathies (TMAs) represent distinct pathological and clinical entities with known chronicity and recurrence. Kidney biopsy is the gold standard to diagnose TMA in patients with renal manifestations, but the prognostic significance of acute or chronic phase of the disease has not been well studied. We examined the clinical characteristics, management, and predictors of acute versus chronic TMA among native and transplants.</p><p><strong>Methods: </strong>Observational, cross-sectional study of a 22-year period at Johns Hopkins Hospital. Prevalence of acute versus chronic TMA was based on specific histology identified on native and allograft kidney biopsies. Predictors of acute and chronic TMA were assessed using simple linear regression and odds ratios.</p><p><strong>Results: </strong>Among 127 patients, 29 (23%) had chronic TMA and 98 (77%) had acute TMA, with 60% female and 43 ± 18 years of age. Chronic TMA was significantly associated with a history of lupus or hemolytic uremic syndrome (HUS) and the use of clopidogrel or mammalian target of rapamycin inhibitors (mTORi). Specifically, chronic TMA was significantly associated with use of mTORi in native kidneys. The odds of chronic TMA compared to acute TMA were lower for each race (Caucasians, 76%; blacks, 38%; Hispanics and Asians, 22%).</p><p><strong>Conclusions: </strong>A kidney biopsy may not necessarily be needed to determine the presence of chronic TMA since certain predictors, as those demonstrated by our study (use of mTORi and history of lupus or HUS), independently predicted higher odds of developing chronic TMA and its sequelae conditions.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"309-317"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982231","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}