Cynthia Lim, Ru Sin Lim, Jason Choo, Esther Huimin Leow, Gek Cher Chan, Yaochun Zhang, Jun Li Ng, Hui-Lin Chin, Ee Shien Tan, Jeannette Goh, Naline Gandhi, Yong Hong Ng, Mya Than, Indra Ganesan, Siew Le Chong, Celeste Yap, Sing Ming Chao, Breana Cham, Sylvia Kam, Jiin Ying Lim, Irene Mok, Hui Zhuan Tan, Jia Liang Kwek, Tung Lin Lee, Ziyin Wang, Su Mein Goh, Regina Lim, See Cheng Yeo, Boon Wee Teo, Yi Da, David Matchar, Kar Hui Ng
{"title":"Clinical Implementation of Nephrologist-Led Genomic Testing for Glomerular Diseases in Singapore: Rationale and Protocol.","authors":"Cynthia Lim, Ru Sin Lim, Jason Choo, Esther Huimin Leow, Gek Cher Chan, Yaochun Zhang, Jun Li Ng, Hui-Lin Chin, Ee Shien Tan, Jeannette Goh, Naline Gandhi, Yong Hong Ng, Mya Than, Indra Ganesan, Siew Le Chong, Celeste Yap, Sing Ming Chao, Breana Cham, Sylvia Kam, Jiin Ying Lim, Irene Mok, Hui Zhuan Tan, Jia Liang Kwek, Tung Lin Lee, Ziyin Wang, Su Mein Goh, Regina Lim, See Cheng Yeo, Boon Wee Teo, Yi Da, David Matchar, Kar Hui Ng","doi":"10.1159/000542942","DOIUrl":"10.1159/000542942","url":null,"abstract":"<p><strong>Introduction: </strong>The early diagnosis and appropriate treatment of monogenic glomerular diseases can reduce kidney failure, avoid unnecessary investigations such as kidney biopsies and ineffective treatment with immunosuppressants, guide transplant decisions, and inform the genetic risks of their family members. Yet, genetic testing for kidney disease is underutilized in Singapore. We aimed to implement a nephrologist-led genetic service and evaluate the acceptance, adoption, utility, and cost-effectiveness of genetic testing for monogenic glomerular disease in Singapore.</p><p><strong>Methods: </strong>We will perform a prospective, multi-centre, type II hybrid effectiveness-implementation study with a post-design to evaluate both implementation and clinical outcomes of nephrologist-led genetic testing for suspected genetic glomerular kidney diseases. The multi-disciplinary implementation team will train \"genetic nephrologists\" to provide pre- and post-test counselling, order targeted exome panel sequencing for suspected glomerular kidney diseases (persistent microscopic haematuria and/or albuminuria or proteinuria in the absence of known causes, steroid-resistant primary nephrotic syndrome, apparent familial IgA nephropathy, or chronic kidney disease with no apparent cause), and interpret genetic test results; create workflows for patient referral, evaluation and management, and discuss genetic results at regular genomic board meetings. The outcomes are acceptance, appropriateness and adoption among patients and nephrologists, utility (proportion of patients who received genetic testing and have a confirmed diagnosis of genetic glomerular disease), and cost-effectiveness.</p><p><strong>Conclusion: </strong>This study will create and evaluate a nephrologist-led genetic service, develop an efficient variant curation process, and inform future recommendations on the optimal referral and genetic testing strategy for monogenic glomerular disease in Singapore. This will facilitate the future mainstreaming of genetic testing that will enable precision medicine in kidney care.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"158-171"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765481","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}
Ana I Raya, Angela Vidal, Ignacio López, Mariano Rodríguez, Escolástico Aguilera-Tejero, Carmen Pineda
{"title":"Phosphorus Restriction Prevents Rapamycin-Induced Kidney Damage in Rats.","authors":"Ana I Raya, Angela Vidal, Ignacio López, Mariano Rodríguez, Escolástico Aguilera-Tejero, Carmen Pineda","doi":"10.1159/000541411","DOIUrl":"10.1159/000541411","url":null,"abstract":"<p><strong>Introduction: </strong>There are conflicting reports about the effect or rapamycin on the kidneys. Rapamycin is known to promote phosphaturia that may be associated to renal injury.</p><p><strong>Methods: </strong>Detailed histopathological studies were performed on the kidneys of rats with normal (control) and reduced (Nx) renal mass that were treated with rapamycin (1.3 mg/kg for 22 days) or placebo. The effect of rapamycin was also evaluated in control and Nx rats fed different amounts of phosphorus: 0.6% P (NP), 1.2% P (HP), and 0.2% P (LP). Quantitative scores of kidney lesions were obtained for interstitial nephritis (IN), tubular damage (TD), and nephrocalcinosis (NC).</p><p><strong>Results: </strong>When compared with placebo, rapamycin administration to Nx rats resulted in significant increases in IN (4.17 ± 0.74 vs. 1.51 ± 0.53%) and TD (14.45 ± 1.51 vs. 8.61 ± 1.83%). Rapamycin also increased NC both in control (0.86 ± 0.23 vs. 0.14 ± 0.06%) and Nx (0.86 ± 0.32 vs. 0.15 ± 0.14%) rats. In control rats receiving rapamycin, feeding HP aggravated IN (3.25 ± 0.48%), TD (22.47 ± 4.56%), and NC (3.66 ± 0.75%), while feeding LP prevented development of any renal lesions. In Nx rats treated with rapamycin, HP intake also increased IN (8.95 ± 1.94%), TD (26.86 ± 3.95%), and NC (2.77 ± 0.60%), whereas feeding LP reduced all lesions to lower levels than in rats fed NP. Rapamycin treatment increased fractional excretion of P (FEP), and an excellent correlation between scores for renal lesions and FEP was found.</p><p><strong>Conclusion: </strong>Rapamycin has deleterious effects on kidney pathology causing lesions that are located mainly at tubular and tubulointerstitial level. Rapamycin-induced kidney damage is more evident in rats that already have decreased renal function and seems to be related to the phosphaturic effect of the drug. Dietary P restriction prevents kidney damage in rats treated with rapamycin.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"48-57"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387299","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}
Yuxin Lin, Yixuan Pan, Quan Han, Jianhang Xu, Junni Wang, Xin Lei, Liangliang Chen, Yaomin Wang, Pingping Ren, Lan Lan, Jianghua Chen, Fei Han
{"title":"Obinutuzumab May Be an Effective and Safe Option for Adult Minimal Change Disease and Focal Segmental Glomerulosclerosis Patients after Multitarget Therapy Including Rituximab.","authors":"Yuxin Lin, Yixuan Pan, Quan Han, Jianhang Xu, Junni Wang, Xin Lei, Liangliang Chen, Yaomin Wang, Pingping Ren, Lan Lan, Jianghua Chen, Fei Han","doi":"10.1159/000541972","DOIUrl":"10.1159/000541972","url":null,"abstract":"<p><strong>Introduction: </strong>Rituximab has proven effective and safe in pediatric and adult minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) patients with frequently relapsing nephrotic syndrome. However, its efficacy diminishes in several patients who experience nephrotic syndrome relapsing in short durations or failing to achieve remission. We aimed to explore the efficacy and safety of obinutuzumab, a novel anti-CD20 antibody, in these patients.</p><p><strong>Methods: </strong>A retrospective case series study at our center included 11 adult MCD or FSGS patients who presented with nephrotic syndrome characterized by short-duration relapses or lack of remission after multitarget therapy, including rituximab. Primary outcomes included the first relapse-free time, relapse rate during follow-up, and the use of immunosuppressants after obinutuzumab. All adverse events were recorded.</p><p><strong>Results: </strong>Eleven adult patients (median age 26.0 years, 81.9% males) received an average obinutuzumab dose of 2.0 (1.0, 2.0) g during a median follow-up period of 17.0 (12.0, 22.0) months. The first relapse-free time was 12.1 (10.8, 18.9) months. Two patients with FSGS experienced relapses, while the remaining maintained remission by the end of follow-up. Six patients (54.5%) achieved cessation of corticosteroids and immunosuppressants within 3 months after obinutuzumab. Adverse events were mostly mild.</p><p><strong>Conclusion: </strong>Obinutuzumab may be an efficient and safe option for inducing remission in adult MCD and FSGS patients who presented with nephrotic syndrome relapsing in short durations or failed to achieve remission after multitarget therapy, including rituximab. It was effective in maintaining remission in MCD patients, while its efficacy in maintaining remission in FSGS patients remained uncertain.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"111-120"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455857","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":"Trends and the Role of Gene-Environment Interactions in Idiopathic Membranous Nephropathy in Northern China.","authors":"Wanyin Hou, Sufang Shi, Zhe Yan, Maodong Liu, Gengxin Guo, Yujing Zhang, Yun Dong, Junjie Gao, Fuyun Sun, Guicai Hu, Zhaoxia Zheng, Liping Duan, Haisong Zhang, Bing Liu, Shaomei Li, Sumin Jiao, Jinwei Wang, Zhao Cui, Suxia Wang, Ying Li, Shuxia Fu, Minghui Zhao","doi":"10.1159/000542910","DOIUrl":"10.1159/000542910","url":null,"abstract":"<p><strong>Introduction: </strong>Idiopathic membranous nephropathy (iMN) has become one of the most prevalent primary glomerular diseases, with a marked increase in prevalence over the past two decades in northern China. Fine particulate matter (PM2.5) is considered to be associated with this rising prevalence. In this study, we aimed to evaluate the trends of iMN in relation to improved air quality and conduct a cross-sectional study in Hebei province (northern China, near Beijing) to investigate the role of gene-environment interactions in its development.</p><p><strong>Methods: </strong>This study established two cohorts. Cohort 1 included 22,937 pathology reports from Peking University First Hospital (2002-2021) to assess iMN prevalence. Cohort 2 comprised 5,635 iMN patients from 11 cities in Hebei province (2009-2013). DNA samples from 374 iMN patients and 1,259 controls were genotyped for SNPs rs4664608 (PLA2R1) and rs2187668 (HLA-DQA1). Patients were stratified by air pollution risk levels. The annual percentage change (APC) and average annual percentage change were estimated using a joinpoint regression model. Gene-environment interactions were analyzed using logistic regression and epinet calculation.</p><p><strong>Results: </strong>In cohort 1, 5,586 patients with iMN were identified, representing 24.3% of the 22,937 patients from 2002 to 2021. The general population showed a significant increase in iMN proportion with an APC of +12.7% per year from 2002 to 2014 (95% CI: 10.3-17.5, p < 0.001), followed by a decline with an APC of -5.6% per year from 2014 to 2021 (95% CI: -9.6 to -2.6, p < 0.001). In Hebei province, the iMN frequency rose significantly with an APC of +17.6% per year from 2002 to 2016 (95% CI: 14.5-28.6, p < 0.001), peaking at 60%, and then declined with an APC of -5.5% per year from 2016 to 2021 (95% CI: -13.1 to -1.2, p = 0.02). Cohort 2 highlighted significant regional variation in iMN incidence across Hebei province. Geographic exposure to pollution was identified as an independent risk factor for iMN (RR: 1.49, 95% CI: 1.38-1.56, p < 0.001). Gene-environment interaction analysis revealed that patients with risk alleles in the PLA2R1 gene and exposure to risk environments had a markedly increased risk of developing iMN (odds ratio = 38.72, 95% CI: 11.95-125.46, p < 0.01).</p><p><strong>Conclusion: </strong>The annual growth rate of iMN in northern China appears to be slowing down. Gene-environment interactions may have contributed to the previously observed increase in prevalence.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"148-157"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765397","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}
John J Sim, Qiaoling Chen, Nancy Cannizzaro, Simran K Bhandari, Ancilla W Fernandes, John Chang, Cibele Pinto, Asher D Schachter, Mohit Mathur
{"title":"Incidence of Adult Primary Immunoglobulin A Nephropathy among a Racially/Ethnically Diverse Population in the United States.","authors":"John J Sim, Qiaoling Chen, Nancy Cannizzaro, Simran K Bhandari, Ancilla W Fernandes, John Chang, Cibele Pinto, Asher D Schachter, Mohit Mathur","doi":"10.1159/000541869","DOIUrl":"10.1159/000541869","url":null,"abstract":"<p><strong>Introduction: </strong>IgA nephropathy (IgAN), a leading cause of kidney failure worldwide, is one of the most common forms of primary glomerulonephropathy with variability by race and ethnicity. Using a diverse cohort within a large integrated health system in the United States (US), we identified and characterized patients with biopsy-proven IgAN and report annual incidence rates across racial/ethnic groups and standardized to the US nationally.</p><p><strong>Methods: </strong>A cross-sectional study between January 1, 2010, and December 31, 2021 within Kaiser Permanente Southern California was performed. Patients (age >/=18 years) who underwent a native kidney biopsy and identified as having primary IgAN comprised the study population. Laboratory, demographic, and comorbidity information were obtained from the electronic health records. Annual incidence rates were calculated for biopsy-proven IgAN (per 100,000 person-years) and standardized to 2020 US Census.</p><p><strong>Results: </strong>Of 9,392 individuals who underwent kidney biopsy, 606 adult patients were identified with primary IgAN. Crude annual IgAN incidence rates ranged from 1.3 to 2.2 (per 100,000 person-years). US census standardized incidence rate (CI) of IgAN was 1.4 (0.8, 2.0) per 100,000 person-years in the 12-year period. Incidence rate (per 100,000 person-years) was highest among Asian/Pacific Islander (4.5) and Hispanic (1.7) patients and lowest among White (1.2) and Black (0.6) patients. Median estimated glomerular filtration rate (eGFR) was 51 mL/min with median urine protein creatinine ratio (uPCR) 1.8 g/g.</p><p><strong>Conclusion: </strong>Among a large diverse US population within Southern California, we observed an IgAN incidence rate of 1.7 which estimated to a standardized US incidence of 1.4 (per 100,000 person-years) within a 12-year period. Patients appear to be diagnosed at more advanced disease given kidney function and proteinuria at biopsy.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"172-177"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575069","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}
Hui Chen, Long The Nguyen, Min Feng, Baoming Wang, Bai Xu, Rochelle A Yarak, Yik Lung Chan, Seethalakshmi Viswanathan, Muralikrishna Gangadharan Komala, Carol A Pollock, Brian G Oliver, Sonia Saad
{"title":"Cross-Generational Impact of Maternal Exposure to Low Level of PM2.5 on Kidney Health.","authors":"Hui Chen, Long The Nguyen, Min Feng, Baoming Wang, Bai Xu, Rochelle A Yarak, Yik Lung Chan, Seethalakshmi Viswanathan, Muralikrishna Gangadharan Komala, Carol A Pollock, Brian G Oliver, Sonia Saad","doi":"10.1159/000542135","DOIUrl":"10.1159/000542135","url":null,"abstract":"<p><strong>Introduction: </strong>Inhaled fine and ultrafine particulate matter may affect organs other than the lung, including the kidney. Recent studies have consistently shown the possibility of air pollution in highly polluted countries to be nephrotoxic. However, in countries like Australia, where air quality generally adheres to or remains below the WHO standards, the subtle yet consequential impacts of chronic exposure to seemingly safe levels of traffic PM2.5, are a subject of increasing significance. However, how such exposures in the peri-pregnancy period affect kidney health in mothers and the offspring is unclear, which formed the aims of this study.</p><p><strong>Methods: </strong>Female Balb/c mice were exposed to PM2.5 (5 μg/day) delivered nasally for 6 weeks prior to mating, during gestation and lactation (PM group). In a subgroup, PM2.5 was switched to saline from mating until offspring were weaned to model mothers moving to areas with clean air. Kidneys were analysed in dams and adult offspring at 13 weeks of age.</p><p><strong>Results: </strong>PM2.5 induced oxidative stress without histological changes in the dam's kidney. However, male PM offspring displayed in utero underdevelopment, characterised by reduced body weight and kidney-to-body weight at birth compared to control offspring, and lower glomerular numbers, with a marked increase in albuminuria, glomerulosclerosis, inflammation, oxidative stress, and mitochondrial injury. Female PM offspring had delayed postnatal development, lower glomerular numbers, increased glomerulosclerosis, and oxidative stress injury markers. Removal of PM2.5 from conception significantly reduced DNA oxidation and kidney damage in the offspring.</p><p><strong>Conclusion: </strong>There is no safe level of ambient PM2.5 for kidney health when exposed in utero. Maternal PM2.5 exposure equally impacts the kidney health of male and female offspring. Removal of PM2.5 from conception was overall protective to the offspring.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"222-235"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685825","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}
Cheol Ho Park, Hyunsun Lim, Youn Nam Kim, Jae Young Kim, Hyung Woo Kim, Tae Ik Chang, Seung Hyeok Han
{"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}
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
{"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}
Priscila Aparecida Correa Freitas, Yasmini Dandara Silva da Silva, José Antonio Tesser Poloni, Francisco José Veríssimo Veronese, Luiz Felipe Santos Goncalves
{"title":"The Clinical Impact of Urinalysis Screened by Automated Microscopy Compared to Reference Manual Analysis.","authors":"Priscila Aparecida Correa Freitas, Yasmini Dandara Silva da Silva, José Antonio Tesser Poloni, Francisco José Veríssimo Veronese, Luiz Felipe Santos Goncalves","doi":"10.1159/000541561","DOIUrl":"10.1159/000541561","url":null,"abstract":"<p><strong>Introduction: </strong>Clinical laboratories have replaced conventional manual urine microscopy with automated urinalysis; however, concerns persist regarding its validity in detecting specific elements of urinary sediment crucial for evaluating kidney diseases. This study aimed to assess the accuracy of urinary sediment analysis performed by a large hospital laboratory compared to a standardized microscopic review, focusing on patients both with and without kidney disease.</p><p><strong>Methods: </strong>Urine samples were randomly selected from routine laboratory specimens at a university hospital. Laboratory analysis was performed using LabUmat 2 and Urised 3 PRO equipment (Abbott Diagnostics). In the automated analysis for sediment examination, technicians have the option to reclassify urinary sediment elements as necessary and, if warranted, conduct manual microscopic evaluations to validate findings. The laboratory's analysis was compared with a \"reference\" analysis, which was double-blinded and conducted by two experienced technicians using bright-field and phase-contrast microscopy.</p><p><strong>Results: </strong>503 samples were selected, with 52.3% originating from nephrology outpatient clinic patients. Overall agreement between the laboratory results and the reference analysis was 42.1%. The sensitivity (SN) of the laboratory examination for detecting pathological casts, lipiduria, and renal tubular epithelial cells was low (<50%), while specificity (SP) was high (>98%). However, for hyaline casts (SN: 50.4%; SP: 80.9%) and dysmorphic red blood cells (SN: 62.3%; SP: 96.2%), accuracy was intermediate. Performance was better for hematuria (SN: 86.1%; SP: 82.3%; intraclass correlation coefficient [ICC]: 0.703; R: 0.828) and leukocyturia (SN: 84.9%; SP: 95.1%; ICC: 0.807; R: 0.861). In patients with kidney disease (N = 248) and in samples manually reviewed by the laboratory (N = 115), accuracy for each urinary element was comparable to the overall sample findings. However, when assessing the ability to identify elements suggestive of nephropathy, only samples manually reviewed by the laboratory showed statistically similar results to those obtained by the reference analysis (p = 0.503, McNemar's test).</p><p><strong>Conclusion: </strong>Employing automated urinalysis seems to be accurate for detecting hematuria and leukocyturia, as well as for screening patients without kidney diseases. However, clinical laboratories attending complex patients should employ personalized strategies to help decide when to perform manual review, thus avoiding misleading urinalysis results.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"178-186"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455858","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}
Guizhen Yu, Xuliang Wang, Yijie Cheng, Suhan Zhou, Yan Yang, Jun Cheng, Heng Li, Xiayu Li, Fei Han, Jianghua Chen
{"title":"Urinary Sodium Excretion and Kidney Disease Progression in IgA Nephropathy: A Cohort Study.","authors":"Guizhen Yu, Xuliang Wang, Yijie Cheng, Suhan Zhou, Yan Yang, Jun Cheng, Heng Li, Xiayu Li, Fei Han, Jianghua Chen","doi":"10.1159/000540270","DOIUrl":"10.1159/000540270","url":null,"abstract":"<p><strong>Introduction: </strong>The role of dietary sodium intake in the risk of chronic kidney disease progression remains controversial. This study aimed to evaluate the association of urinary sodium excretion and progression of IgA nephropathy.</p><p><strong>Methods: </strong>We assessed 596 patients with IgA nephropathy, and urinary sodium excretion was measured at the time of kidney biopsy. Cox proportional hazards models and restricted cubic splines were used to assess the association between urinary sodium excretion and kidney disease progression events, defined as 50% eGFR decline or development of kidney failure.</p><p><strong>Results: </strong>After a mean follow-up of 58.9 months, a total of 75 (12.6%) participants of IgA nephropathy reached composite kidney disease progression events. The risk of kidney disease progression events was higher in patients with higher urinary sodium excretion. After adjustment for traditional risk factors, higher levels of ln-transformed urinary sodium excretion was associated with the kidney disease progression events in patients with IgA nephropathy (HR: 2.1; 95% CI: 1.4-3.2). In reference to the first tertile of urinary sodium excretion, hazard ratios were 1.9 (95% CI: 1.0-3.4) for the second tertile and 2.1 (95% CI: 1.1-3.9) for the third tertile.</p><p><strong>Conclusion: </strong>Higher levels of urinary sodium excretion were associated with kidney disease progression events in IgA nephropathy independent of clinical and biopsy characteristics.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"85-93"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339174","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}