Renzo Mignani, Gian Marco Berti, Gisella Vischini, Roberta Di Costanzo, Francesca Ciurli, Daniele Vetrano, Elena Biagini, Serena Serratore, Benedetta Fabbrizio, Gianandrea Pasquinelli, Gaetano La Manna, Irene Capelli
{"title":"N215S基因型法布里肾病的功能和组织病理学相关性。","authors":"Renzo Mignani, Gian Marco Berti, Gisella Vischini, Roberta Di Costanzo, Francesca Ciurli, Daniele Vetrano, Elena Biagini, Serena Serratore, Benedetta Fabbrizio, Gianandrea Pasquinelli, Gaetano La Manna, Irene Capelli","doi":"10.1186/s13023-025-03994-9","DOIUrl":null,"url":null,"abstract":"<p><strong>Rationale & objective: </strong>Late-onset Anderson-Fabry disease appears in adulthood, usually with prevalent cardiac involvement. The N215S (p.Asn215Ser) missense mutation represents the most frequent late-onset variant in European countries. The N215S nephropathy was then investigated from a clinical and histopathological point of view.</p><p><strong>Study design: </strong>Renal and cardiac assessments were evaluated at baseline. The standardized scoring system of histologic involvement proposed by International Study Group of Fabry Nephropathy was applied to kidney biopsies, performed before the treatment start. A deeper digital histological reinterpretation was provided in a subgroup. Treated patients' renal function was evaluated at diagnosis (T0), after 5 years (T1) and after 10 years (T2) from the treatment start.</p><p><strong>Setting & participants: </strong>27 patients (11 males, 16 female) with a N215S variant were evaluated.</p><p><strong>Findings: </strong>Mean eGFR at diagnosis was 84.98 ± 26.4 mL/min/1.73m<sup>2</sup>, and 6 patients were CKD-stage 3-5. In the 24 treated patients, the mean T0 eGFR was 86.5 ± 28.01 mL/min/1.73m<sup>2</sup>; 26% with CKD-stage 3-5 (mean eGFR 45.3 ± 19.4 mL/min/1.73m<sup>2</sup>). At T1, the mean eGFR in 14/24 patients was 69.1 mL/min/1.73m<sup>2</sup> and 35% with CKD-stage 3-5 (mean eGFR 33.3 ± 17.1 mL/min/1.73m<sup>2</sup>). T2 was evaluated in 6 patients, of which 5/6 (85%) with CKD-stage 3 (mean eGFR 43.2 ± 20 mL/min/1.73m<sup>2</sup>). 18/18 patients presented kidney biopsies with different degrees of podocyte vacuolization, while sclerosis was documented in 9/18. 14/18 patients showed a higher podocyte vacuolization score. Males showed significant greater interstitial fibrosis (p 0.016). Arteriolar intimal fibrosis significantly correlated with eGFR at baseline (p 0.09).</p><p><strong>Limitations: </strong>The main limitation was the number of patients, as well as the number of available kidney and cardiac biopsies.</p><p><strong>Conclusions: </strong>Even at early stages, N215S patients display typical histological abnormalities of Fabry disease. Moreover, chronic kidney disease seems to progress over time in treated patients, with arterial and arteriolar intimal fibrosis.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"468"},"PeriodicalIF":3.5000,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12403288/pdf/","citationCount":"0","resultStr":"{\"title\":\"Functional and histopathologic correlation in the fabry nephropathy with N215S genotype.\",\"authors\":\"Renzo Mignani, Gian Marco Berti, Gisella Vischini, Roberta Di Costanzo, Francesca Ciurli, Daniele Vetrano, Elena Biagini, Serena Serratore, Benedetta Fabbrizio, Gianandrea Pasquinelli, Gaetano La Manna, Irene Capelli\",\"doi\":\"10.1186/s13023-025-03994-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Rationale & objective: </strong>Late-onset Anderson-Fabry disease appears in adulthood, usually with prevalent cardiac involvement. The N215S (p.Asn215Ser) missense mutation represents the most frequent late-onset variant in European countries. The N215S nephropathy was then investigated from a clinical and histopathological point of view.</p><p><strong>Study design: </strong>Renal and cardiac assessments were evaluated at baseline. The standardized scoring system of histologic involvement proposed by International Study Group of Fabry Nephropathy was applied to kidney biopsies, performed before the treatment start. A deeper digital histological reinterpretation was provided in a subgroup. Treated patients' renal function was evaluated at diagnosis (T0), after 5 years (T1) and after 10 years (T2) from the treatment start.</p><p><strong>Setting & participants: </strong>27 patients (11 males, 16 female) with a N215S variant were evaluated.</p><p><strong>Findings: </strong>Mean eGFR at diagnosis was 84.98 ± 26.4 mL/min/1.73m<sup>2</sup>, and 6 patients were CKD-stage 3-5. In the 24 treated patients, the mean T0 eGFR was 86.5 ± 28.01 mL/min/1.73m<sup>2</sup>; 26% with CKD-stage 3-5 (mean eGFR 45.3 ± 19.4 mL/min/1.73m<sup>2</sup>). At T1, the mean eGFR in 14/24 patients was 69.1 mL/min/1.73m<sup>2</sup> and 35% with CKD-stage 3-5 (mean eGFR 33.3 ± 17.1 mL/min/1.73m<sup>2</sup>). T2 was evaluated in 6 patients, of which 5/6 (85%) with CKD-stage 3 (mean eGFR 43.2 ± 20 mL/min/1.73m<sup>2</sup>). 18/18 patients presented kidney biopsies with different degrees of podocyte vacuolization, while sclerosis was documented in 9/18. 14/18 patients showed a higher podocyte vacuolization score. Males showed significant greater interstitial fibrosis (p 0.016). Arteriolar intimal fibrosis significantly correlated with eGFR at baseline (p 0.09).</p><p><strong>Limitations: </strong>The main limitation was the number of patients, as well as the number of available kidney and cardiac biopsies.</p><p><strong>Conclusions: </strong>Even at early stages, N215S patients display typical histological abnormalities of Fabry disease. Moreover, chronic kidney disease seems to progress over time in treated patients, with arterial and arteriolar intimal fibrosis.</p>\",\"PeriodicalId\":19651,\"journal\":{\"name\":\"Orphanet Journal of Rare Diseases\",\"volume\":\"20 1\",\"pages\":\"468\"},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2025-09-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12403288/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Orphanet Journal of Rare Diseases\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s13023-025-03994-9\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Orphanet Journal of Rare Diseases","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13023-025-03994-9","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
Functional and histopathologic correlation in the fabry nephropathy with N215S genotype.
Rationale & objective: Late-onset Anderson-Fabry disease appears in adulthood, usually with prevalent cardiac involvement. The N215S (p.Asn215Ser) missense mutation represents the most frequent late-onset variant in European countries. The N215S nephropathy was then investigated from a clinical and histopathological point of view.
Study design: Renal and cardiac assessments were evaluated at baseline. The standardized scoring system of histologic involvement proposed by International Study Group of Fabry Nephropathy was applied to kidney biopsies, performed before the treatment start. A deeper digital histological reinterpretation was provided in a subgroup. Treated patients' renal function was evaluated at diagnosis (T0), after 5 years (T1) and after 10 years (T2) from the treatment start.
Setting & participants: 27 patients (11 males, 16 female) with a N215S variant were evaluated.
Findings: Mean eGFR at diagnosis was 84.98 ± 26.4 mL/min/1.73m2, and 6 patients were CKD-stage 3-5. In the 24 treated patients, the mean T0 eGFR was 86.5 ± 28.01 mL/min/1.73m2; 26% with CKD-stage 3-5 (mean eGFR 45.3 ± 19.4 mL/min/1.73m2). At T1, the mean eGFR in 14/24 patients was 69.1 mL/min/1.73m2 and 35% with CKD-stage 3-5 (mean eGFR 33.3 ± 17.1 mL/min/1.73m2). T2 was evaluated in 6 patients, of which 5/6 (85%) with CKD-stage 3 (mean eGFR 43.2 ± 20 mL/min/1.73m2). 18/18 patients presented kidney biopsies with different degrees of podocyte vacuolization, while sclerosis was documented in 9/18. 14/18 patients showed a higher podocyte vacuolization score. Males showed significant greater interstitial fibrosis (p 0.016). Arteriolar intimal fibrosis significantly correlated with eGFR at baseline (p 0.09).
Limitations: The main limitation was the number of patients, as well as the number of available kidney and cardiac biopsies.
Conclusions: Even at early stages, N215S patients display typical histological abnormalities of Fabry disease. Moreover, chronic kidney disease seems to progress over time in treated patients, with arterial and arteriolar intimal fibrosis.
期刊介绍：
Orphanet Journal of Rare Diseases is an open access, peer-reviewed journal that encompasses all aspects of rare diseases and orphan drugs. The journal publishes high-quality reviews on specific rare diseases. In addition, the journal may consider articles on clinical trial outcome reports, either positive or negative, and articles on public health issues in the field of rare diseases and orphan drugs. The journal does not accept case reports.
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