RESUMO
APOL1 variants have been associated with renal phenotypes in blacks. To refine clinical outcomes and discover mechanisms of APOL1-associated kidney injury, we analyzed clinical and genomic datasets derived from 90 black subjects in the Nephrotic Syndrome Study Network (NEPTUNE), stratified by APOL1 risk genotype. Ninety subjects with proteinuria ≥0.5 g/d were enrolled at first biopsy for primary nephrotic syndrome and followed. Clinical outcomes were determined, and renal histomorphometry and sequencing of Mendelian nephrotic syndrome genes were performed. APOL1 variants were genotyped, and glomerular and tubulointerstitial transcriptomes from protocol renal biopsy cores were analyzed for differential and correlative gene expression. Analyses were performed under the recessive model (high-risk genotype defined by two risk alleles). APOL1 high-risk genotype was significantly associated with a 17 ml/min per 1.73 m(2) lower eGFR and a 69% reduction in the probability of complete remission at any time, independent of histologic diagnosis. Neither APOL1 risk group was enriched for Mendelian mutations. On renal biopsy, high-risk genotype was associated with increased fractional interstitial area, interstitial fibrosis, and tubular atrophy. Risk genotype was not associated with intrarenal APOL1 mRNA expression levels. Differential expression analysis demonstrated an increased steady-state level of five genes associated with the high-risk genotype (CXCL9, CXCL11, and UBD in glomerulus; SNOR14B and MUC13 in tubulointerstitium). APOL1 tubulointerstitial coexpression analysis showed coexpression of APOL1 mRNA levels with a group of intrarenal transcripts that together were associated with increased interstitial fibrosis and tubular atrophy. These data indicate the high-risk APOL1 genotype confers renal risk across histopathologic diagnoses.
Assuntos
Apolipoproteínas/genética , Negro ou Afro-Americano/genética , Genômica/métodos , Túbulos Renais/patologia , Lipoproteínas HDL/genética , Síndrome Nefrótica/genética , Síndrome Nefrótica/patologia , Adolescente , Adulto , Alelos , Apolipoproteína L1 , Atrofia/genética , Biópsia , Quimiocina CXCL11/genética , Quimiocina CXCL9/genética , Criança , Feminino , Fibrose , Expressão Gênica , Genótipo , Taxa de Filtração Glomerular/genética , Humanos , Glomérulos Renais/fisiopatologia , Túbulos Renais/metabolismo , Túbulos Renais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Mucinas/genética , Síndrome Nefrótica/fisiopatologia , Proteinúria/genética , RNA Mensageiro/metabolismo , Fatores de Risco , Transcriptoma , Ubiquitinas/genética , Adulto JovemRESUMO
PROBLEM: Reflective practice is necessary for self-regulated learning. Helping medical students develop these skills can be challenging since they are difficult to observe. One common solution is to assign students' reflective self-assessments, which produce large quantities of narrative assessment data. Reflective self-assessments also provide feedback to faculty regarding students' understanding of content, reflective abilities, and areas for course improvement. To maximize student learning and feedback to faculty, reflective self-assessments must be reviewed and analyzed, activities that are often difficult for faculty due to the time-intensive and cumbersome nature of processing large quantities of narrative assessment data. APPROACH: The authors collected narrative assessment data (2,224 students' reflective self-assessments) from 344 medical students' reflective self-assessments. In academic years 2019-2020 and 2021-2022, students at the University of Cincinnati College of Medicine responded to 2 prompts (aspects that surprised students, areas for student improvement) after reviewing their standardized patient encounters. These free-text entries were analyzed using TopEx, an open-source natural language processing (NLP) tool, to identify common topics and themes, which faculty then reviewed. OUTCOMES: TopEx expedited theme identification in students' reflective self-assessments, unveiling 10 themes for prompt 1 such as question organization and history analysis, and 8 for prompt 2, including sensitive histories and exam efficiency. Using TopEx offered a user-friendly, time-saving analysis method without requiring complex NLP implementations. The authors discerned 4 education enhancement implications: aggregating themes for future student reflection, revising self-assessments for common improvement areas, adjusting curriculum to guide students better, and aiding faculty in providing targeted upcoming feedback. NEXT STEPS: The University of Cincinnati College of Medicine aims to refine and expand the utilization of TopEx for deeper narrative assessment analysis, while other institutions may model or extend this approach to uncover broader educational insights and drive curricular advancements.