Clinical chemistry最新文献_第9页

Urine Cell-Free RNA vs Plasma Cell-Free RNA for Monitoring of Kidney Injury and Immune Complications. 尿无细胞RNA与血浆无细胞RNA监测肾损伤和免疫并发症。

IF 9.3 2区医学

Clinical chemistry Pub Date : 2025-08-12 DOI: 10.1093/clinchem/hvaf082

Omary Mzava,Glory Feyisayo Agun,Conor J Loy,Isabel Helena Gonzalez-Bocco,Liz-Audrey Djomnang Kounatse,Andrew Bliss,Sophia L Wells,Joan Lenz,Emma Belcher,Kaiwen Chen,Sophia Koo,Lindsey Robert Baden,Tinyi Chu,Matthew Pellan Cheng,Jerome Ritz,Shruti Gupta,Iwijn De Vlaminck

{"title":"Urine Cell-Free RNA vs Plasma Cell-Free RNA for Monitoring of Kidney Injury and Immune Complications.","authors":"Omary Mzava,Glory Feyisayo Agun,Conor J Loy,Isabel Helena Gonzalez-Bocco,Liz-Audrey Djomnang Kounatse,Andrew Bliss,Sophia L Wells,Joan Lenz,Emma Belcher,Kaiwen Chen,Sophia Koo,Lindsey Robert Baden,Tinyi Chu,Matthew Pellan Cheng,Jerome Ritz,Shruti Gupta,Iwijn De Vlaminck","doi":"10.1093/clinchem/hvaf082","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf082","url":null,"abstract":"BACKGROUNDThere is increasing interest in the use of circulating cell-free RNA (cfRNA) in plasma as an analyte for diagnosing and monitoring disease. While it is known that cfRNA can also be isolated from urine, the diagnostic potential of urine cfRNA, particularly relative to plasma cfRNA, remains underexplored.METHODSMatched plasma and urine were collected from hematopoietic stem cell transplant (HSCT) recipients (n = 24), immune-checkpoint-inhibitor (ICI) recipients with or without acute kidney injury (AKI) (n = 46), and healthy volunteers (n = 5), yielding 297 samples. Unbiased cfRNA sequencing was performed, followed by comparison of molecular diversity, tissue and cellular origin, and diagnostic performance for systemic (HSCT) and renal (AKI) complications.RESULTSUrine and plasma cfRNA displayed distinct molecular composition and cellular origin across all groups. In HSCT, pronounced changes in plasma cfRNA were detected during the course of treatment, while urine cfRNA changes were minimal. Conversely, when comparing ICI recipients with and without AKI, cfRNA signatures indicative of disease and AKI etiology were observed in urine but not in plasma. These urine-derived signatures included injury markers and immune transcripts consistent with localized renal inflammation.CONCLUSIONSThis study reveals the distinct origin and diagnostic utility of plasma and urine cfRNA and suggests urine cfRNA is a promising analyte to monitor kidney injury, especially in the context of AKI following ICI treatment.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"4 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Allelic Cataloging of RHD–RHCE Reference Sequences Using Targeted Long-Read Sequencing RHD-RHCE参考序列的靶向长读测序等位基因编目

IF 9.3 2区医学

Clinical chemistry Pub Date : 2025-08-12 DOI: 10.1093/clinchem/hvaf090

Junhyup Song, Soon Sung Kwon, Eun Jung Suh, Hyun Kyung Kim, Jong Rak Choi, Dae-Hyun Ko, Sinyoung Kim

{"title":"Allelic Cataloging of RHD–RHCE Reference Sequences Using Targeted Long-Read Sequencing","authors":"Junhyup Song, Soon Sung Kwon, Eun Jung Suh, Hyun Kyung Kim, Jong Rak Choi, Dae-Hyun Ko, Sinyoung Kim","doi":"10.1093/clinchem/hvaf090","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf090","url":null,"abstract":"Background Implementation of blood group genotyping has offered substantial benefits in transfusion medicine. However, the complex molecular basis of Rh antigen expression and a high degree of sequence homology between RHD and RHCE have long limited the accuracy of blood group genotyping, highlighting the need for a more systematic characterization of existing molecular variations. Methods We employed a custom target enrichment strategy to perform high-fidelity (HiFi) long-read sequencing of the RHD–RHCE region on chromosome 1 in samples obtained from 63 individuals. The resulting HiFi long-read sequences were aligned to the human reference genome GRCh38, variants were identified and phased, and allelic reference sequences were generated. Phylogenetic analyses were then performed to classify RHD–RHCE alleles and elucidate their evolutionary relationships. Results Our approach enabled the phasing of heterozygous variants at distant loci, as well as precise characterization of tandem repeat variations and structural variants. Complete phase resolution was achieved in 76.2% of samples, yielding 96 allelic reference sequences spanning the entire RHD–RHCE region. Alleles within each phylogenetic clade exhibited a characteristic sequence pattern spanning RHD to RHCE. Conclusions Our findings revealed that the current Eurasian allelic pool originated from 2 distinct primordial lineages, with occasional interallelic recombination events shaping the present-day RHD–RHCE haplotype diversity. While most previous classification approaches have treated RHD and RHCE independently, our results support the notion that analyzing them as a single evolutionary unit may offer practical advantages for molecular typing approaches.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"166 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Noninvasive Prenatal Testing: Mosaic Ratio Score as a Predictor for Confined Placental Mosaicism. 无创产前检测：镶嵌比评分作为局限性胎盘镶嵌的预测因子。

IF 9.3 2区医学

Clinical chemistry Pub Date : 2025-08-07 DOI: 10.1093/clinchem/hvaf095

Jasper Linthorst,Erik A Sistermans

引用次数: 0

Gene Therapy for Hemophilias: Opportunities and Challenges for the Clinical Laboratory. 血友病基因治疗：临床实验室的机遇与挑战。

IF 9.3 2区医学

Clinical chemistry Pub Date : 2025-08-07 DOI: 10.1093/clinchem/hvaf085

Armando Tripodi,Isabella Garagiola,Niccolò Bitto,Vincenzo La Mura,Flora Peyvandi

{"title":"Gene Therapy for Hemophilias: Opportunities and Challenges for the Clinical Laboratory.","authors":"Armando Tripodi,Isabella Garagiola,Niccolò Bitto,Vincenzo La Mura,Flora Peyvandi","doi":"10.1093/clinchem/hvaf085","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf085","url":null,"abstract":"BACKGROUNDHemophilia A and B are X-linked coagulation disorders characterized by low or dysfunctional Factor VIII (FVIII) or IX (FIX), respectively. Currently, hemophilia A and B are treated by FVIII/FIX replacement therapy with plasma-derived or recombinant products or by FVIII-mimetic agents (e.g., emicizumab). More recently, gene therapy (GT) has been developed and licensed for use in patients.CONTENTIn recent years, adeno-associated viral vectors (AAVV) have been developed as a means to transfer genetic material into liver cells. Clinical trials of patients with hemophilia A or B have shown that GT is effective at sustaining plasma levels of FVIII/FIX and reducing bleeding. Important issues must be considered with GT, including the gene, the delivery method, the target organ, and the measurement of the FVIII/IX produced thereafter.SUMMARYSeveral conclusions can be drawn about GT in hemophilia A and B based on the literature and clinical practice. First, relevant gene material (FVIII/FIX) can be incorporated into AAVV, which is then infused into patients. AAVV targets liver cells and produces FVIII/IX. Second, the selection of patients who should be free from liver disease is paramount for successful therapy. Third transgene factors can be measured by one-stage clotting (OSA) or chromogenic assays (CA). Based on results from clinical trials, OSA measures transgene factor levels that are approximately 2 times higher than CA. Although expert opinions favor the OSA for transgene FIX and CA for transgene FVIII, no firm evidence is yet available on which method is better associated with clinical outcomes.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"11 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

eGFR Inaccuracy in the Assessment of Living Kidney Transplant Donor Eligibility. eGFR在活体肾移植供者资格评估中的不准确性。

IF 6.3 2区医学

Clinical chemistry Pub Date : 2025-08-01 DOI: 10.1093/clinchem/hvaf071

Sarrah Lahorewala, Zheng Yin, Jacob Kinskey, Shane A Bobart, Angelina Edwards, Paul Christensen, Roger L Bertholf, Xin Yi

{"title":"eGFR Inaccuracy in the Assessment of Living Kidney Transplant Donor Eligibility.","authors":"Sarrah Lahorewala, Zheng Yin, Jacob Kinskey, Shane A Bobart, Angelina Edwards, Paul Christensen, Roger L Bertholf, Xin Yi","doi":"10.1093/clinchem/hvaf071","DOIUrl":"10.1093/clinchem/hvaf071","url":null,"abstract":"Background: Accurate glomerular filtration rate (GFR) estimation is crucial for evaluating living kidney donors, especially when measured GFR (mGFR) is unavailable. This study compares the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), full age spectrum (FAS), and European Kidney Function Consortium (EKFC) creatinine- and/or cystatin C-based estimated GFR (eGFR) equations against iohexol mGFR to determine the optimal equation for donor eligibility assessment in a US population.Methods: 1210 kidney donor candidates were retrospectively analyzed, comparing eGFR equations based on creatinine, cystatin C, or both against iohexol mGFR. Accuracy metrics (P10, P30, mean bias) and subgroup analyses for Black donors and age-based bias were evaluated. The classification performance of eGFR equations in donor eligibility was examined.Results: The 2021 CKD-EPIcr [AS (age, sex)] demonstrated the best accuracy across the overall cohort (P10 48.2%, P30 93.2%, mean bias -4.8 mL/min/1.73 m²). The 2021 CKD-EPIcr-cys (AS) excelled in Black donors (P10 60.3%, P30 95.4%, mean bias -3.6 mL/min/1.73 m²). Cystatin C-based equations showed higher negative bias, with the largest underestimation observed in older donors. All equations demonstrated <35% positive predictive value (PPV) for rejecting ineligible donors (<60 mL/min/1.73 m²) but >85% PPV in determining acceptable donors (≥90 mL/min/1.73 m²). Overall, 2021 CKD-EPIcr-cys (AS) was the most reliable for identifying acceptable donors (F1 score 83.9 at ≥90 mL/min/1.73 m²). Using age/sex-specific thresholds improved performance of all equations in donor eligibility classification compared to absolute thresholds.Conclusions: No eGFR equation reliably rejected ineligible donors. 2021 CKD-EPIcr-cys (AS) exhibited the best overall performance for donor eligibility assessment.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":"870-883"},"PeriodicalIF":6.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Toward Improved Prostate Cancer Screening: Insights from the Göteborg-2 Trial. 改善前列腺癌筛查：Göteborg-2试验的启示

IF 6.3 2区医学

Clinical chemistry Pub Date : 2025-08-01 DOI: 10.1093/clinchem/hvaf032

Jacob E Tallman, Sigrid V Carlsson, Hans Lilja

引用次数: 0

An Ambiguous NUDT15 Signal in a Child with B-cell Acute Lymphoblastic Leukemia. 一个模糊的NUDT15信号在儿童b细胞急性淋巴细胞白血病。

IF 9.3 2区医学

Clinical chemistry Pub Date : 2025-08-01 DOI: 10.1093/clinchem/hvaf028

Rosalie M Sterner,Farha Sherani,Margaret A DiGuardo,Patricia T Greipp,Ann M Moyer

引用次数: 0

Discordance between Cystatin C-Based and Creatinine-Based Estimated Glomerular Filtration Rate as a Measure of Health. 基于胱抑素c和基于肌酐的肾小球滤过率作为健康指标之间的不一致。