Pub Date : 2024-09-01DOI: 10.1016/j.ekir.2024.06.028
Introduction
Among individuals with high-risk APOL1 genotypes, the lifetime risk of developing kidney failure is ∼15%, indicating that other genetic variants or nongenetic modifiers likely contribute substantially to an individual patient’s risk of progressive kidney disease. Here, we estimate the prevalence and distribution of Mendelian kidney diseases among patients with high-risk APOL1 genotypes undergoing commercial genetic testing in the United States.
Methods
We analyzed clinical exome sequencing data from 15,181 individuals undergoing commercial genetic testing for Mendelian kidney disease in the United States from 2020 to 2021. We identified patients with high-risk APOL1 genotypes by the presence of G1/G1, G1/G2, or G2/G2 alleles. Patients carrying single risk APOL1 alleles were identified as G1/G0, G2/G0; the remainder of patients were G0/G0. We estimated the prevalence and distribution of Mendelian kidney disease stratified by APOL1 genotype and genetically predicted ancestry.
Results
Of 15,181 patients, 3119 had genetic testing results consistent with a molecular diagnosis of Mendelian kidney disease (20.5%). Of 15,181 patients, 1035 (6.8%) had high-risk APOL1 genotypes. Among patients with recent genomic African ancestry, the prevalence of Mendelian kidney diseases was lower in those with high-risk APOL1 genotypes (9.6%; n = 91/944) compared with single risk APOL1 allele carriers (13.6%; n = 198/1453) and those with G0/G0 APOL1 genotypes (16.6%; n = 213/1281). Among patients with Mendelian kidney disease and recent genomic African ancestry, we observed differences in the prevalence of pathogenic/likely pathogenic variants in PKD1 (19.8% in high-risk vs. 30.2% in low-risk genotypes), and COL4A4 (24.2% in high-risk vs. 10.5% in low-risk genotypes).
Conclusion
In this selected population of patients undergoing clinical genetic testing, we found evidence of Mendelian kidney disease in ∼10% patients with high-risk APOL1 genotypes.
{"title":"Prevalence of Mendelian Kidney Disease Among Patients With High-Risk APOL1 Genotypes Undergoing Commercial Genetic Testing in the United States","authors":"","doi":"10.1016/j.ekir.2024.06.028","DOIUrl":"10.1016/j.ekir.2024.06.028","url":null,"abstract":"<div><h3>Introduction</h3><p>Among individuals with high-risk <em>APOL1</em> genotypes, the lifetime risk of developing kidney failure is ∼15%, indicating that other genetic variants or nongenetic modifiers likely contribute substantially to an individual patient’s risk of progressive kidney disease. Here, we estimate the prevalence and distribution of Mendelian kidney diseases among patients with high-risk <em>APOL1</em> genotypes undergoing commercial genetic testing in the United States.</p></div><div><h3>Methods</h3><p>We analyzed clinical exome sequencing data from 15,181 individuals undergoing commercial genetic testing for Mendelian kidney disease in the United States from 2020 to 2021. We identified patients with high-risk <em>APOL1</em> genotypes by the presence of G1/G1, G1/G2, or G2/G2 alleles. Patients carrying single risk APOL1 alleles were identified as G1/G0, G2/G0; the remainder of patients were G0/G0. We estimated the prevalence and distribution of Mendelian kidney disease stratified by <em>APOL1</em> genotype and genetically predicted ancestry.</p></div><div><h3>Results</h3><p>Of 15,181 patients, 3119 had genetic testing results consistent with a molecular diagnosis of Mendelian kidney disease (20.5%). Of 15,181 patients, 1035 (6.8%) had high-risk <em>APOL1</em> genotypes. Among patients with recent genomic African ancestry, the prevalence of Mendelian kidney diseases was lower in those with high-risk <em>APOL1</em> genotypes (9.6%; <em>n</em> = 91/944) compared with single risk <em>APOL1</em> allele carriers (13.6%; <em>n</em> = 198/1453) and those with G0/G0 <em>APOL1</em> genotypes (16.6%; <em>n</em> = 213/1281). Among patients with Mendelian kidney disease and recent genomic African ancestry, we observed differences in the prevalence of pathogenic/likely pathogenic variants in <em>PKD1</em> (19.8% in high-risk vs. 30.2% in low-risk genotypes), and <em>COL4A4</em> (24.2% in high-risk vs. 10.5% in low-risk genotypes).</p></div><div><h3>Conclusion</h3><p>In this selected population of patients undergoing clinical genetic testing, we found evidence of Mendelian kidney disease in ∼10% patients with high-risk <em>APOL1</em> genotypes.</p></div>","PeriodicalId":17761,"journal":{"name":"Kidney International Reports","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2468024924018059/pdfft?md5=b29d18a87ba4bd548ac28b602ad80060&pid=1-s2.0-S2468024924018059-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141552442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01DOI: 10.1016/j.ekir.2024.06.018
Introduction
Primary membranous nephropathy (PMN) is most often caused by autoantibodies to phospholipase A2 receptor (PLA2R). M-PLACE (NCT04145440) is an open-label, phase 1b/2a study that assessed the safety and efficacy of the fully human anti-CD38 monoclonal antibody felzartamab in high-risk anti-PLA2R+ PMN.
Methods
Patients with newly diagnosed or relapsed PMN (cohort 1 [C1]; n = 18) or PMN refractory to immunosuppressive therapy (IST) (cohort 2 [C2]; n = 13) received 9 infusions of felzartamab 16 mg/kg in the 24-week treatment period, followed by a 28-week follow-up. The primary end point was the incidence and severity of treatment-emergent adverse events (TEAEs).
Results
A total of 31 patients were enrolled and received felzartamab. Twenty-seven patients (87.1%) had TEAEs, including infusion-related reactions (IRRs) (29.0%), hypogammaglobulinemia (25.8%), peripheral edema (19.4%), and nausea (16.1%). Five patients (16.1%) had serious TEAEs that all resolved. Immunologic response (anti-PLA2R titer reduction ≥50%) was achieved by 20 of 26 efficacy-evaluable patients (76.9%) (C1, 13/15 [86.7%]; C2, 7/11 [63.6%]). Anti-PLA2R titer reductions were rapid (week 1 response, 44.0%; response 7 months after last felzartamab dose [end of study, EOS], 53.8%). Partial proteinuria remission (urine protein-to-creatinine ratio [UPCR] reduction ≥50%, UPCR <3.0 g/g, and stable estimated glomerular filtration rate [eGFR]) was achieved by 9 of 26 patients (34.6%) (C1, 7/15 [46.7%]; C2, 2/11 [18.2%]) before or at EOS (median follow-up, 366 days). Serum albumin increased from baseline to EOS in 20 of 26 patients (76.9%) (C1, 12/15 [80.0%]; C2, 8/11 [72.7%]).
Conclusion
In this population with high-risk anti-PLA2R+ PMN, felzartamab was tolerated and resulted in rapid partial and complete immunologic responses and partial improvements in proteinuria and serum albumin in some patients.
{"title":"Phase 1b/2a Study Assessing the Safety and Efficacy of Felzartamab in Anti-Phospholipase A2 Receptor Autoantibody–Positive Primary Membranous Nephropathy","authors":"","doi":"10.1016/j.ekir.2024.06.018","DOIUrl":"10.1016/j.ekir.2024.06.018","url":null,"abstract":"<div><h3>Introduction</h3><p>Primary membranous nephropathy (PMN) is most often caused by autoantibodies to phospholipase A2 receptor (PLA2R). M-PLACE (NCT04145440) is an open-label, phase 1b/2a study that assessed the safety and efficacy of the fully human anti-CD38 monoclonal antibody felzartamab in high-risk anti-PLA2R+ PMN.</p></div><div><h3>Methods</h3><p>Patients with newly diagnosed or relapsed PMN (cohort 1 [C1]; <em>n</em> = 18) or PMN refractory to immunosuppressive therapy (IST) (cohort 2 [C2]; <em>n</em> = 13) received 9 infusions of felzartamab 16 mg/kg in the 24-week treatment period, followed by a 28-week follow-up. The primary end point was the incidence and severity of treatment-emergent adverse events (TEAEs).</p></div><div><h3>Results</h3><p>A total of 31 patients were enrolled and received felzartamab. Twenty-seven patients (87.1%) had TEAEs, including infusion-related reactions (IRRs) (29.0%), hypogammaglobulinemia (25.8%), peripheral edema (19.4%), and nausea (16.1%). Five patients (16.1%) had serious TEAEs that all resolved. Immunologic response (anti-PLA2R titer reduction ≥50%) was achieved by 20 of 26 efficacy-evaluable patients (76.9%) (C1, 13/15 [86.7%]; C2, 7/11 [63.6%]). Anti-PLA2R titer reductions were rapid (week 1 response, 44.0%; response 7 months after last felzartamab dose [end of study, EOS], 53.8%). Partial proteinuria remission (urine protein-to-creatinine ratio [UPCR] reduction ≥50%, UPCR <3.0 g/g, and stable estimated glomerular filtration rate [eGFR]) was achieved by 9 of 26 patients (34.6%) (C1, 7/15 [46.7%]; C2, 2/11 [18.2%]) before or at EOS (median follow-up, 366 days). Serum albumin increased from baseline to EOS in 20 of 26 patients (76.9%) (C1, 12/15 [80.0%]; C2, 8/11 [72.7%]).</p></div><div><h3>Conclusion</h3><p>In this population with high-risk anti-PLA2R+ PMN, felzartamab was tolerated and resulted in rapid partial and complete immunologic responses and partial improvements in proteinuria and serum albumin in some patients.</p></div>","PeriodicalId":17761,"journal":{"name":"Kidney International Reports","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2468024924017947/pdfft?md5=1262fd0f8075a83d159984724ba5abb6&pid=1-s2.0-S2468024924017947-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141547504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01DOI: 10.1016/j.ekir.2024.06.034
José Luis Cobo-Sánchez , Ian Blanco-Mavillard , Raquel Pelayo-Alonso , Noelia Mancebo-Salas , Ismael Fernández-Fernández , Irene Larrañeta-Inda , Ana Ulzurrun-García , Isidro Sánchez-Villar , Fernando González-García , Julia Hernando-García , Ma Jesús Rollán-de la Sota , Luís Miguel Vieira-Barbosa Lopes , Ma del Rosario Prieto-Rebollo , Carolina Sesmero-Ramos , Catalina Jaume-Riutort , Rafael Casas-Cuesta , Mateo Alcántara-Crespo , Joan Ernest de Pedro-Gómez
Introduction
Exit-site infections (ESI) of central venous catheters for hemodialysis (CVC-HD) has been associated with early catheter removal and an increased risk of CVC-HD related bacteremia. No specific clinical scales to predict ESI have previously been validated.
Methods
A multicenter prospective cohort study was performed to validate the proposed scale, which is based on the following 5 signs and symptoms: (i) pain at exit site during interdialytic period; (ii) hyperemia or erythema ≥2 cm from exit site; (iii) inflammation, induration, or swelling at exit site; (iv) fever ≥38 °C not attributable to other causes, and (v) obvious abscess or purulent exudate at the exit site. Adult patients with a tunneled CVC-HD for at least 1 month after insertion has been included. During each hemodialysis session, the exit site was assessed with the proposed scale by nurses. If any item was present, a pericatheter skin swab culture was collected: positive results were gold standard. The scale was validated using receiver operating characteristic (ROC) curves and logistic regression analysis. For this purpose, the logit function was applied, and the ESI probability calculated, as elogit ESI/1 + elogit ESI.
Results
Three hundred thirty-seven CVC-HDs from 310 patients were analyzed, producing 515 cultures (117 infected and 398 healthy). The final version of the scale includes the following 3 signs and symptoms, which present the greatest predictive capacity: (i) pain at exit site during interdialytic period, (ii) hyperemia or erythema ≥2 cm from exit site, and (iii) abscess or purulent exudate at the exit site. The final version generated an area under the ROC curve (AUC) of 88.3% (95% confidence interval [CI]: 85.2%–91%; P < 0.001), Youden index 0.7557 ≈ 1, sensitivity 80.34% (95% CI: 71.36%–87.71%) and specificity 95.23% (95% CI: 92.73%–97%).
Conclusions
The validation shows that the scale has good predictive properties, detecting approximately 90% of ESI with very acceptable validity parameters.
{"title":"Validation of a Clinical Scale for Early Detection of Infections at the Exit Site of Central Venous Catheters for Hemodialysis","authors":"José Luis Cobo-Sánchez , Ian Blanco-Mavillard , Raquel Pelayo-Alonso , Noelia Mancebo-Salas , Ismael Fernández-Fernández , Irene Larrañeta-Inda , Ana Ulzurrun-García , Isidro Sánchez-Villar , Fernando González-García , Julia Hernando-García , Ma Jesús Rollán-de la Sota , Luís Miguel Vieira-Barbosa Lopes , Ma del Rosario Prieto-Rebollo , Carolina Sesmero-Ramos , Catalina Jaume-Riutort , Rafael Casas-Cuesta , Mateo Alcántara-Crespo , Joan Ernest de Pedro-Gómez","doi":"10.1016/j.ekir.2024.06.034","DOIUrl":"10.1016/j.ekir.2024.06.034","url":null,"abstract":"<div><h3>Introduction</h3><p>Exit-site infections (ESI) of central venous catheters for hemodialysis (CVC-HD) has been associated with early catheter removal and an increased risk of CVC-HD related bacteremia. No specific clinical scales to predict ESI have previously been validated.</p></div><div><h3>Methods</h3><p>A multicenter prospective cohort study was performed to validate the proposed scale, which is based on the following 5 signs and symptoms: (i) pain at exit site during interdialytic period; (ii) hyperemia or erythema ≥2 cm from exit site; (iii) inflammation, induration, or swelling at exit site; (iv) fever ≥38 °C not attributable to other causes, and (v) obvious abscess or purulent exudate at the exit site. Adult patients with a tunneled CVC-HD for at least 1 month after insertion has been included. During each hemodialysis session, the exit site was assessed with the proposed scale by nurses. If any item was present, a pericatheter skin swab culture was collected: positive results were gold standard. The scale was validated using receiver operating characteristic (ROC) curves and logistic regression analysis. For this purpose, the logit function was applied, and the ESI probability calculated, as elogit ESI/1 + elogit ESI.</p></div><div><h3>Results</h3><p>Three hundred thirty-seven CVC-HDs from 310 patients were analyzed, producing 515 cultures (117 infected and 398 healthy). The final version of the scale includes the following 3 signs and symptoms, which present the greatest predictive capacity: (i) pain at exit site during interdialytic period, (ii) hyperemia or erythema ≥2 cm from exit site, and (iii) abscess or purulent exudate at the exit site. The final version generated an area under the ROC curve (AUC) of 88.3% (95% confidence interval [CI]: 85.2%–91%; <em>P</em> < 0.001), Youden index 0.7557 ≈ 1, sensitivity 80.34% (95% CI: 71.36%–87.71%) and specificity 95.23% (95% CI: 92.73%–97%).</p></div><div><h3>Conclusions</h3><p>The validation shows that the scale has good predictive properties, detecting approximately 90% of ESI with very acceptable validity parameters.</p></div>","PeriodicalId":17761,"journal":{"name":"Kidney International Reports","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2468024924018114/pdfft?md5=a1bb30766732c10b82c8c12d604a6788&pid=1-s2.0-S2468024924018114-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141779655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Recently, the monoallelic loss-of-function IFT140 variant was identified as a causative gene for autosomal dominant polycystic kidney disease (ADPKD). In patients with polycystic kidneys who have a positive family history, >90% have pathogenic variants in PKD1 or PKD2, whereas only 1% have IFT140. However, approximately 40% of patients with polycystic kidneys without a family history do not have any pathogenic variants in PKD1 and PKD2.
Methods
We conducted a comprehensive genetic analysis of 157 adult patients with polycystic kidneys whose parents did not have evident polycystic kidneys. We sequenced up to 92 genes associated with inherited cystic kidney disease, including IFT140.
Results
Of the 157 patients, 7 (4.5%) presented with monoallelic loss-of-function variants in the IFT140 gene, 51 (32.5%) with pathogenic variants in the PKD1 or PKD2 gene, and 7 (4.5%) with pathogenic variants in other genes related to inherited kidney cystic disease. The proportion of monoallelic loss-of-function IFT140 variants in this cohort was higher than that in previously reported cohorts with polycystic kidneys who had a positive family history. None of the patients with monoallelic loss-of-function IFT140 variants had polycystic liver disease (PLD). Furthermore, patients with IFT140 pathogenic variants had a significantly smaller kidney volume and a remarkably higher estimated glomerular filtration rate (eGFR) than those with PKD1 pathogenic variants (P = 0.01 and 0.03, respectively).
Conclusion
Because the phenotype of polycystic kidneys caused by the IFT140 gene is mild, parental kidney disease may be overlooked. Therefore, patients without a positive family history are more likely to carry pathogenic variants in IFT140.
{"title":"Importance of IFT140 in Patients with Polycystic Kidney Disease Without a Family History","authors":"Takuya Fujimaru , Takayasu Mori , Akinari Sekine , Motoko Chiga , Shintaro Mandai , Hiroaki Kikuchi , Yutaro Mori , Yu Hara , Tamami Fujiki , Fumiaki Ando , Koichiro Susa , Soichiro Iimori , Shotaro Naito , Ryoichi Hanazawa , Akihiro Hirakawa , Toshio Mochizuki , Tatsuya Suwabe , Yoshifumi Ubara , Shinichi Uchida , Eisei Sohara","doi":"10.1016/j.ekir.2024.06.021","DOIUrl":"10.1016/j.ekir.2024.06.021","url":null,"abstract":"<div><h3>Introduction</h3><p>Recently, the monoallelic loss-of-function IFT140 variant was identified as a causative gene for autosomal dominant polycystic kidney disease (ADPKD). In patients with polycystic kidneys who have a positive family history, >90% have pathogenic variants in <em>PKD1</em> or <em>PKD2</em>, whereas only 1% have <em>IFT140</em>. However, approximately 40% of patients with polycystic kidneys without a family history do not have any pathogenic variants in <em>PKD1</em> and <em>PKD2</em>.</p></div><div><h3>Methods</h3><p>We conducted a comprehensive genetic analysis of 157 adult patients with polycystic kidneys whose parents did not have evident polycystic kidneys. We sequenced up to 92 genes associated with inherited cystic kidney disease, including <em>IFT140</em>.</p></div><div><h3>Results</h3><p>Of the 157 patients, 7 (4.5%) presented with monoallelic loss-of-function variants in the <em>IFT140</em> gene, 51 (32.5%) with pathogenic variants in the <em>PKD1</em> or <em>PKD2</em> gene, and 7 (4.5%) with pathogenic variants in other genes related to inherited kidney cystic disease. The proportion of monoallelic loss-of-function <em>IFT140</em> variants in this cohort was higher than that in previously reported cohorts with polycystic kidneys who had a positive family history. None of the patients with monoallelic loss-of-function <em>IFT140</em> variants had polycystic liver disease (PLD). Furthermore, patients with <em>IFT140</em> pathogenic variants had a significantly smaller kidney volume and a remarkably higher estimated glomerular filtration rate (eGFR) than those with <em>PKD1</em> pathogenic variants (<em>P</em> = 0.01 and 0.03, respectively).</p></div><div><h3>Conclusion</h3><p>Because the phenotype of polycystic kidneys caused by the <em>IFT140</em> gene is mild, parental kidney disease may be overlooked. Therefore, patients without a positive family history are more likely to carry pathogenic variants in <em>IFT140</em>.</p></div>","PeriodicalId":17761,"journal":{"name":"Kidney International Reports","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2468024924017972/pdfft?md5=32c6c7c3e56f588bf020fd36e875b0a6&pid=1-s2.0-S2468024924017972-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141713045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01DOI: 10.1016/j.ekir.2024.06.022
{"title":"Certain Red Yeast Rice Supplements in Japan Cause Acute Tubulointerstitial Injury","authors":"","doi":"10.1016/j.ekir.2024.06.022","DOIUrl":"10.1016/j.ekir.2024.06.022","url":null,"abstract":"","PeriodicalId":17761,"journal":{"name":"Kidney International Reports","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2468024924017984/pdfft?md5=77826395768a3c81afcec47860ccfc49&pid=1-s2.0-S2468024924017984-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141552443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01DOI: 10.1016/j.ekir.2024.06.007
Introduction
Recent technological advancements allowed the development of engaging technological tools. Using ASN funding from the ASN, we developed a 3D Virtual Reality (VR) physiology course entitled DiAL-Neph (Diuretic Action and eLectrolyte transport in the Nephron). We hereby present its evaluation.
Methods
The study consisted of 2 parts: evaluation of knowledge gain, and qualitative evaluation of platform reception. Internal medicine PGY1 residents were randomly assigned into 2 groups: a VR group and a conventional group. Knowledge acquisition was assessed with a post-test administered at the end of the course and repeated within 6 to 12 weeks. Independent t-tests were used to compare the number of correct answers between the groups. A survey and focus groups composed of medicine residents evaluated the platform. Sessions were recorded and transcribed verbatim. Data was analyzed through the content analysis approach by two independent reviewers.
Results
Of 117 PGY1 resident participants, 64 were randomized to the VR group and 53 were randomized to the traditional group. Initial test results showed higher scores among VR compared to the traditional group (76.5% correct vs. 68.8%). Seventy-eight PGY1s participated in the follow up testing (46 VR group vs. 32 traditional group) and results showed no significant difference in test results. Greater than 90% of the residents rated the platform positively and 77% preferred it as a teaching method.
Conclusion
The DiAL-Neph VR platform appeared to improve short-term learning but not long-term retention. Further studies are needed to investigate the impact of such teaching platforms on overall interest in nephrology.
{"title":"Virtual Nephron: Evaluation of a Novel Virtual Reality Educational Tool","authors":"","doi":"10.1016/j.ekir.2024.06.007","DOIUrl":"10.1016/j.ekir.2024.06.007","url":null,"abstract":"<div><h3>Introduction</h3><p>Recent technological advancements allowed the development of engaging technological tools. Using ASN funding from the ASN, we developed a 3D Virtual Reality (VR) physiology course entitled DiAL-Neph (Diuretic Action and eLectrolyte transport in the Nephron). We hereby present its evaluation.</p></div><div><h3>Methods</h3><p>The study consisted of 2 parts: evaluation of knowledge gain, and qualitative evaluation of platform reception. Internal medicine PGY1 residents were randomly assigned into 2 groups: a VR group and a conventional group. Knowledge acquisition was assessed with a post-test administered at the end of the course and repeated within 6 to 12 weeks. Independent t-tests were used to compare the number of correct answers between the groups. A survey and focus groups composed of medicine residents evaluated the platform. Sessions were recorded and transcribed verbatim. Data was analyzed through the content analysis approach by two independent reviewers.</p></div><div><h3>Results</h3><p>Of 117 PGY1 resident participants, 64 were randomized to the VR group and 53 were randomized to the traditional group. Initial test results showed higher scores among VR compared to the traditional group (76.5% correct vs. 68.8%). Seventy-eight PGY1s participated in the follow up testing (46 VR group vs. 32 traditional group) and results showed no significant difference in test results. Greater than 90% of the residents rated the platform positively and 77% preferred it as a teaching method.</p></div><div><h3>Conclusion</h3><p>The DiAL-Neph VR platform appeared to improve short-term learning but not long-term retention. Further studies are needed to investigate the impact of such teaching platforms on overall interest in nephrology.</p></div>","PeriodicalId":17761,"journal":{"name":"Kidney International Reports","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2468024924017662/pdfft?md5=c77befb4d84a218ec78338b4cde66fe2&pid=1-s2.0-S2468024924017662-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141390008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01DOI: 10.1016/j.ekir.2024.07.019
Manuel A. Anderegg , Jan Halbritter
{"title":"Sporadic ADPKD-IFT140: Absence of Family History as an Indicator of Clinical Mildness","authors":"Manuel A. Anderegg , Jan Halbritter","doi":"10.1016/j.ekir.2024.07.019","DOIUrl":"10.1016/j.ekir.2024.07.019","url":null,"abstract":"","PeriodicalId":17761,"journal":{"name":"Kidney International Reports","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2468024924018497/pdfft?md5=0622a7a948cf95928058634e08e3d5a2&pid=1-s2.0-S2468024924018497-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141847254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01DOI: 10.1016/j.ekir.2024.07.002
Cindy Varga , Felix Eichinger , Viji Nair , Abhijit S. Naik , Samih H. Nasr , Agnes B. Fogo , Denis Toskic , Matthias Kretzler , Raymond L. Comenzo
Introduction
There is an unmet need to understand the mechanisms by which amyloid deposition drives alterations in the kidney. We leveraged renal biopsies from amyloid light-chain (AL) amyloidosis participants of the Renal AL Amyloid Involvement and NEOD00 (RAIN) trial (NCT03168906) to perform transcriptional profiling and to employ a novel histologic scoring tool. Our objective was to utilize a transcriptome-driven approach to identify AL molecular signatures that may be prognostic.
Methods
Clinical data were correlated to histologic and molecular findings. A composite scarring injury and amyloid score (AS) were assigned to each biopsy. Glomerular and tubulointerstitial (TI) compartments were microdissected and sequenced separately. Expression data were compared to healthy living donors and focal segmental glomerulosclerosis (FSGS) profiles. Differentially expressed genes were determined.
Results
Cluster analysis revealed 2 distinct patient clusters (G1 and G2) based on gene expression. The AS was higher in the TI compartment (6.5 vs. 4.5; P = 0.0290) of G2. Glomeruli showed activation of fibrotic pathways and increased canonical signaling of LPS/IL-1. TNF activation was noted in TI. Enriched ingenuity canonical pathways included “coagulation system,” “GADD45 signaling,” and “Wnt/Ca+ pathway,” among others. For AL versus living donors, ingenuity pathway analysis identified enrichment in PI3K/Akt signaling. Gene regulators of cellular proliferation were enriched in the amyloid group.
Conclusion
Despite the small sample size, we identified 2 distinct groups of patients with AL based on molecular signatures. Detailed studies of a larger cohort encompassing omics technologies at a single cell resolution will further help to identify the response of individual kidney cell types to amyloid deposits, potentially leading to the development of novel therapeutic targets.
导言：了解淀粉样蛋白沉积驱动肾脏改变的机制是一项尚未得到满足的需求。我们利用淀粉样轻链（AL）淀粉样变性参与肾AL淀粉样变性和NEOD00（RAIN）试验（NCT03168906）的肾活检组织进行转录组分析，并采用一种新型组织学评分工具。我们的目标是利用转录组驱动的方法来识别可能具有预后意义的 AL 分子特征。对每份活检样本进行瘢痕损伤和淀粉样蛋白综合评分（AS）。对肾小球和肾小管间质（TI）进行显微解剖并分别测序。将表达数据与健康供体和局灶节段性肾小球硬化症（FSGS）概况进行比较。结果聚类分析显示，根据基因表达，有两个不同的患者群（G1 和 G2）。G2患者TI区的AS较高（6.5 vs. 4.5; P = 0.0290）。肾小球显示出纤维化途径的激活和 LPS/IL-1 信号的增加。TI中出现TNF激活。丰富的巧妙典型通路包括 "凝血系统"、"GADD45 信号传导 "和 "Wnt/Ca+ 通路 "等。对于AL与活体供体，萌发通路分析确定了PI3K/Akt信号的富集。尽管样本量较小，但我们根据分子特征确定了两组不同的 AL 患者。在单细胞分辨率下对更大样本群进行包含全息技术的详细研究，将进一步帮助确定单个肾细胞类型对淀粉样蛋白沉积的反应，从而有可能开发出新型治疗靶点。
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Pub Date : 2024-09-01DOI: 10.1016/j.ekir.2024.06.037
Gary Tan , Daniel W. Ross
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