A Prospective Study on Complement Activation Distinguishes Focal Segmental Glomerulosclerosis from Minimal Change Disease
Introduction: Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are related podocytopathies with distinct kidney outcomes. Surprisingly, elevated urinary activation fragments have been found in FSGS despite little complement deposition on immunofluorescence (IF) staining. Wh...
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Elsevier
2024-03-01
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| Series: | Kidney International Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2468024923016376 |
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| author | Alexandra Cambier Natacha Patey Virginie Royal François Gougeon Dominique S. Genest Soumeya Brachemi Guillaume Bollée Clémence Merlen Arnaud Bonnefoy Anne-Laure Lapeyraque Stéphan Troyanov |
| author_facet | Alexandra Cambier Natacha Patey Virginie Royal François Gougeon Dominique S. Genest Soumeya Brachemi Guillaume Bollée Clémence Merlen Arnaud Bonnefoy Anne-Laure Lapeyraque Stéphan Troyanov |
| author_sort | Alexandra Cambier |
| collection | DOAJ |
| description | Introduction: Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are related podocytopathies with distinct kidney outcomes. Surprisingly, elevated urinary activation fragments have been found in FSGS despite little complement deposition on immunofluorescence (IF) staining. Whether complement activation distinguishes FSGS from MCD, participating in the development of segmental lesions, remains unknown. Methods: We performed an observational study in patients with MCD and FSGS, and proteinuria ≥1 g/g of creatinine. We included both primary and secondary or unknown causes. We compared urinary fragments of terminal pathway activation, sC5b9, and C5a expressed as creatinine ratios, between MCD and FSGS. Results: Patients with FSGS (n = 41) had a serum albumin of 31±10 g/l and proteinuria of 5.1 (2.6–9.1) g/g at sampling, whereas those with MCD (n = 15) had a lower serum albumin (22 ± 9 g/l; P = 0.002), and a proteinuria of 3.8 (1.9–7.7) g/g (P = 0.40). Urinary sC5b9 and C5a were 8.7 (1.7–52.3) and 1.26 (0.45–1.84) μg/mmol of creatinine, respectively in patients with FSGS; compared to 0.8 (0.0–1.5) and 0.06 (0.01–0.15) μg/mmol of creatinine in MCD (P < 0.001), respectively. We found no association between urinary complement fragments and age, estimated glomerular filtration rate (eGFR), or chronic kidney lesions. When analyzing samples with proteinuria ≥ 3 g/g, the c-statistics for urinary sC5b9 and C5a were 0.96 and 1.00, respectively, in differentiating FSGS from MCD. Conclusion: We found no urinary complement activation fragments in MCD, in comparison to FSGS, despite similar levels of proteinuria. This suggests a role for complement activation in the pathogenesis of FSGS and provides an additional tool for distinguishing these 2 entities. |
| format | Article |
| id | doaj-art-d3611fd4db014861a0d551d2c5bc3178 |
| institution | DOAJ |
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| language | English |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
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| series | Kidney International Reports |
| spelling | doaj-art-d3611fd4db014861a0d551d2c5bc31782025-08-20T03:20:30ZengElsevierKidney International Reports2468-02492024-03-019366167010.1016/j.ekir.2023.12.015A Prospective Study on Complement Activation Distinguishes Focal Segmental Glomerulosclerosis from Minimal Change DiseaseAlexandra Cambier0Natacha Patey1Virginie Royal2François Gougeon3Dominique S. Genest4Soumeya Brachemi5Guillaume Bollée6Clémence Merlen7Arnaud Bonnefoy8Anne-Laure Lapeyraque9Stéphan Troyanov10Division of Nephrology, Centre Hospitalier Universitaire Ste-Justine, University of Montreal, Quebec, Canada; Correspondence: Alexandra Cambier, Service de Néphrologie pédiatrique-hémodialyse, centre de recherche du CHU Sainte-Justine, 3175 Chemin de la Côte-Sainte-Catherine, Montréal, Quebec H3T 1C5, Canada.Pathology Department, Centre Hospitalier Universitaire Ste-Justine, University of Montreal, Quebec, CanadaPathology Department, Hôpital Maisonneuve-Rosemont, Quebec, CanadaPathology Department, Centre Hospitalier de l’Université de Montréal, Quebec, CanadaDivision of Nephrology, Hôpital du Sacré-Cœur-de-Montréal, Quebec, CanadaNephrology Division, Centre Hospitalier de l’Université de Montréal, Quebec, CanadaNephrology Division, Centre Hospitalier de l’Université de Montréal, Quebec, CanadaDivision of Hematology, Centre Hospitalier Universitaire Sainte-Justine, University of Montreal, Quebec, CanadaDivision of Hematology, Centre Hospitalier Universitaire Sainte-Justine, University of Montreal, Quebec, CanadaDivision of Nephrology, Centre Hospitalier Universitaire Ste-Justine, University of Montreal, Quebec, CanadaDivision of Nephrology, Hôpital du Sacré-Cœur-de-Montréal, Quebec, Canada; Division of Nephrology, Hôtel-Dieu de St-Jérôme, St-Jerome, Quebec, CanadaIntroduction: Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are related podocytopathies with distinct kidney outcomes. Surprisingly, elevated urinary activation fragments have been found in FSGS despite little complement deposition on immunofluorescence (IF) staining. Whether complement activation distinguishes FSGS from MCD, participating in the development of segmental lesions, remains unknown. Methods: We performed an observational study in patients with MCD and FSGS, and proteinuria ≥1 g/g of creatinine. We included both primary and secondary or unknown causes. We compared urinary fragments of terminal pathway activation, sC5b9, and C5a expressed as creatinine ratios, between MCD and FSGS. Results: Patients with FSGS (n = 41) had a serum albumin of 31±10 g/l and proteinuria of 5.1 (2.6–9.1) g/g at sampling, whereas those with MCD (n = 15) had a lower serum albumin (22 ± 9 g/l; P = 0.002), and a proteinuria of 3.8 (1.9–7.7) g/g (P = 0.40). Urinary sC5b9 and C5a were 8.7 (1.7–52.3) and 1.26 (0.45–1.84) μg/mmol of creatinine, respectively in patients with FSGS; compared to 0.8 (0.0–1.5) and 0.06 (0.01–0.15) μg/mmol of creatinine in MCD (P < 0.001), respectively. We found no association between urinary complement fragments and age, estimated glomerular filtration rate (eGFR), or chronic kidney lesions. When analyzing samples with proteinuria ≥ 3 g/g, the c-statistics for urinary sC5b9 and C5a were 0.96 and 1.00, respectively, in differentiating FSGS from MCD. Conclusion: We found no urinary complement activation fragments in MCD, in comparison to FSGS, despite similar levels of proteinuria. This suggests a role for complement activation in the pathogenesis of FSGS and provides an additional tool for distinguishing these 2 entities.http://www.sciencedirect.com/science/article/pii/S2468024923016376complement activationfocal segmental glomerulosclerosisminimal change diseasenephrotic syndromeproteinuriaurinary complement fragments |
| spellingShingle | Alexandra Cambier Natacha Patey Virginie Royal François Gougeon Dominique S. Genest Soumeya Brachemi Guillaume Bollée Clémence Merlen Arnaud Bonnefoy Anne-Laure Lapeyraque Stéphan Troyanov A Prospective Study on Complement Activation Distinguishes Focal Segmental Glomerulosclerosis from Minimal Change Disease Kidney International Reports complement activation focal segmental glomerulosclerosis minimal change disease nephrotic syndrome proteinuria urinary complement fragments |
| title | A Prospective Study on Complement Activation Distinguishes Focal Segmental Glomerulosclerosis from Minimal Change Disease |
| title_full | A Prospective Study on Complement Activation Distinguishes Focal Segmental Glomerulosclerosis from Minimal Change Disease |
| title_fullStr | A Prospective Study on Complement Activation Distinguishes Focal Segmental Glomerulosclerosis from Minimal Change Disease |
| title_full_unstemmed | A Prospective Study on Complement Activation Distinguishes Focal Segmental Glomerulosclerosis from Minimal Change Disease |
| title_short | A Prospective Study on Complement Activation Distinguishes Focal Segmental Glomerulosclerosis from Minimal Change Disease |
| title_sort | prospective study on complement activation distinguishes focal segmental glomerulosclerosis from minimal change disease |
| topic | complement activation focal segmental glomerulosclerosis minimal change disease nephrotic syndrome proteinuria urinary complement fragments |
| url | http://www.sciencedirect.com/science/article/pii/S2468024923016376 |
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