Fernando Caravaca-Fontán1, Hernando Trujillo2, Marina Alonso3, Montserrat Díaz-Encarnación4, Virginia Cabello5, Gema Ariceta6, Luis F Quintana7, Helena Marco8, Xoana Barros9, Natalia Ramos10, Nuria Rodríguez-Mendiola11, Sonia Cruz12, Gema Fernández-Juárez13, Eva Rodríguez14, Francisco de la Cerda15, Ana Pérez de José16, Inmaculada López17, Loreto Fernández18, Vanessa Pérez Gómez19, Ana Ávila20, Luis Bravo21, Javier Lumbreras22, Natalia Allende23, Maria Dolores Sanchez de la Nieta24, Teresa Olea25, Marta Melgosa26, Ana Huerta27, Rosa Miquel28, Carmen Mon29, Gloria Fraga30, Alberto de Lorenzo31, Juliana Draibe32, Fayna González33, Amir Shabaka34, Maria Luisa Illescas35, Consuelo Calvo36, Victoria Oviedo37, Iara Da Silva4, Elena Goicoechea de Jorge38, Francisco Caravaca39, Manuel Praga40. 1. Instituto de Investigación Hospital 12 de octubre (i+12), Madrid, Spain; Department of Medicine, Universidad Complutense de Madrid, Madrid, Spain. 2. Department of Nephrology, Hospital Universitario 12 de Octubre, Madrid, Spain. 3. Department of Pathology, Hospital Universitario 12 de Octubre, Madrid, Spain. 4. Department of Nephrology, Fundación Puigvert, Barcelona, Spain. 5. Department of Nephrology, Hospital Universitario Virgen del Rocío, Sevilla, Spain. 6. Department of Pediatric Nephrology, Hospital Universitario Vall d'Hebron, Universidad Autónoma de Barcelona, Barcelona, Spain. 7. Department of Nephrology, Hospital Clinic de Barcelona Department of Medicine, University of Barcelona, IDIBAPS, Barcelona, Spain. 8. Department of Nephrology, Hospital Universitario Germans Trias i Pujol, Badalona, Barcelona, Spain. 9. Department of Nephrology, Hospital Universitario Doctor Josep Trueta, Gerona, Spain. 10. Department of Nephrology, Hospital Universitario Vall d'Hebron, Barcelona, Spain. 11. Department of Nephrology, Hospital Universitario Ramón y Cajal, Madrid, Spain. 12. Department of Nephrology, Hospital Universitario Juan Ramón Jiménez, Huelva, Spain. 13. Department of Nephrology, Hospital Universitario Fundación Alcorcón, Alcorcón, Madrid, Spain. 14. Department of Nephrology, Hospital del Mar, Barcelona, Spain. 15. Department of Pediatric Nephrology, Hospital Universitario Virgen del Rocío, Sevilla, Spain. 16. Department of Nephrology, Hospital Universitario Gregorio Marañón, Madrid, Spain. 17. Department of Nephrology, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain. 18. Department of Nephrology, Complejo Hospitalario de Navarra, Navarra, Spain. 19. Department of Nephrology, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain. 20. Department of Nephrology, Hospital Universitario Doctor Peset, Valencia, Spain. 21. Department of Nephrology, Hospital Universitario A Coruña, La Coruña, Spain. 22. Pediatric Nephrology Unit, Hospital Universitario Son Espases, Balearic Islands Health Research Institute (IdISBa), Palma de Mallorca, Spain. 23. Department of Nephrology, Hospital Universitario Son Espases, Palma de Mallorca, Spain. 24. Department of Nephrology, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain. 25. Department of Nephrology, Hospital Universitario La Paz, Madrid, Spain. 26. Department of Pediatric Nephrology, Hospital Universitario La Paz, Madrid, Spain. 27. Department of Nephrology, Hospital Universitario Puerta de Hierro, Madrid, Spain. 28. Department of Nephrology, Hospital Universitario Canarias, Tenerife, Spain. 29. Department of Nephrology, Hospital Universitario Severo Ochoa, Leganés, Madrid, Spain. 30. Department of Pediatric Nephrology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain. 31. Department of Nephrology, Hospital Universitario de Getafe, Madrid, Spain. 32. Department of Nephrology, Hospital Universitario de Bellvitge, Barcelona, Spain. 33. Department of Nephrology, Hospital Doctor Negrín, Gran Canaria, Spain. 34. Department of Nephrology, Hospital Universitario Clínico San Carlos, Madrid, Spain. 35. Department of Nephrology, Complejo Hospitalario Universitario de Albacete, Albacete, Spain. 36. Department of Nephrology, Hospital General Universitario de Castellón, Castellón, Spain. 37. Department of Nephrology, Hospital Universitario Marqués de Valdecilla, Santander, Spain. 38. Department of Immunlogy, Universidad Complutense de Madrid, Madrid, Spain; Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid and Centro de Investigación Biomédica en Red en Enfermedades Raras, Madrid, Spain. 39. Department of Nephrology, Hospital Universitario de Badajoz, Badajoz, Spain. 40. Instituto de Investigación Hospital 12 de octubre (i+12), Madrid, Spain; Department of Medicine, Universidad Complutense de Madrid, Madrid, Spain; Department of Nephrology, Hospital Universitario 12 de Octubre, Madrid, Spain. Electronic address: mpragat@senefro.org.
Abstract
RATIONALE & OBJECTIVE: A previous study that evaluated associations of kidney biopsy findings with disease progression in patients with C3 glomerulopathy (C3G) proposed a prognostic histologic index (C3G-HI) that has not yet been validated. Our objective was to validate the performance of the C3G-HI in a new patient population. STUDY DESIGN: Multicenter, retrospective cohort study. SETTING & PARTICIPANTS: 111 patients fulfilling diagnostic criteria of C3G between January 1995 and December 2019, from 33 nephrology departments belonging to the Spanish Group for the Study of Glomerular Diseases (GLOSEN). PREDICTORS: Demographic, clinical parameters, C3G-HI total activity score, and the C3G-HI total chronicity score. OUTCOME: Time to kidney failure. ANALYTICAL APPROACH: Intraclass correlation coefficients and κ statistic were used to summarize inter-rater reproducibility for assessment of histopathology in kidney biopsies. The nonlinear relationships of risk of kidney failure with the total activity score and total chronicity score were modeled using Cox proportional hazards analysis that incorporated cubic splines. RESULTS: The study group included 93 patients with C3 glomerulonephritis and 18 with dense-deposit disease. Participants had an overall meanage of 35±22 (SD) years. Forty-eight patients (43%) developed kidney failure after a mean follow-up of 65±27 months. The overall inter-rater reproducibility was very good for the total activity score (intraclass correlation coefficient [ICC]=0.63) and excellent for total chronicity score (ICC=0.89). Baseline estimated glomerular filtration rate (eGFR), 24-hour proteinuria, and treatment with immunosuppression were the main determinants of kidney failure in a model with only clinical variables. Only tubular atrophy and interstitial fibrosis were identified as predictors in a model with histological variables. When the total activity score and total chronicity score were added to the model, only the latter was identified as an independent predictor of kidney failure. LIMITATIONS: Only a subset of the kidney biopsies was centrally reviewed. Residual confounding. CONCLUSIONS: We validated the performance of C3G-HI as a predictor of kidney failure in patients with C3G. The total chronicity score was the principal histologic correlate of kidney failure.
RATIONALE & OBJECTIVE: A previous study that evaluated associations of kidney biopsy findings with disease progression in patients with C3 glomerulopathy (C3G) proposed a prognostic histologic index (C3G-HI) that has not yet been validated. Our objective was to validate the performance of the C3G-HI in a new patient population. STUDY DESIGN: Multicenter, retrospective cohort study. SETTING & PARTICIPANTS: 111 patients fulfilling diagnostic criteria of C3G between January 1995 and December 2019, from 33 nephrology departments belonging to the Spanish Group for the Study of Glomerular Diseases (GLOSEN). PREDICTORS: Demographic, clinical parameters, C3G-HI total activity score, and the C3G-HI total chronicity score. OUTCOME: Time to kidney failure. ANALYTICAL APPROACH: Intraclass correlation coefficients and κ statistic were used to summarize inter-rater reproducibility for assessment of histopathology in kidney biopsies. The nonlinear relationships of risk of kidney failure with the total activity score and total chronicity score were modeled using Cox proportional hazards analysis that incorporated cubic splines. RESULTS: The study group included 93 patients with C3 glomerulonephritis and 18 with dense-deposit disease. Participants had an overall meanage of 35±22 (SD) years. Forty-eight patients (43%) developed kidney failure after a mean follow-up of 65±27 months. The overall inter-rater reproducibility was very good for the total activity score (intraclass correlation coefficient [ICC]=0.63) and excellent for total chronicity score (ICC=0.89). Baseline estimated glomerular filtration rate (eGFR), 24-hour proteinuria, and treatment with immunosuppression were the main determinants of kidney failure in a model with only clinical variables. Only tubular atrophy and interstitial fibrosis were identified as predictors in a model with histological variables. When the total activity score and total chronicity score were added to the model, only the latter was identified as an independent predictor of kidney failure. LIMITATIONS: Only a subset of the kidney biopsies was centrally reviewed. Residual confounding. CONCLUSIONS: We validated the performance of C3G-HI as a predictor of kidney failure in patients with C3G. The total chronicity score was the principal histologic correlate of kidney failure.
Authors: Hannah J Lomax-Browne; Nicholas R Medjeral-Thomas; Sean J Barbour; Jack Gisby; Heedeok Han; Andrew S Bomback; Fernando C Fervenza; Thomas H Cairns; Richard Szydlo; Sven-Jean Tan; Stephen D Marks; Aoife M Waters; Gerald B Appel; Vivette D D'Agati; Sanjeev Sethi; Cynthia C Nast; Ingeborg Bajema; Charles E Alpers; Agnes B Fogo; Christoph Licht; Fadi Fakhouri; Daniel C Cattran; James E Peters; H Terence Cook; Matthew C Pickering Journal: Clin J Am Soc Nephrol Date: 2022-07 Impact factor: 10.614
Authors: Hernando Trujillo; Justo Sandino; Teresa Cavero; Fernando Caravaca-Fontán; Eduardo Gutiérrez; Ángel M Sevillano; Amir Shabaka; Gema Fernández-Juárez; Pablo Rodríguez Doyágüez; Rocío Gimena Muñoz; Leonardo Calle García; Virginia Cabello; José Manuel Muñoz-Terol; Ana García Santiago; Oscar Toldos; Juan Antonio Moreno; Manuel Praga Journal: Kidney Int Rep Date: 2022-01-19
Authors: Fernando Caravaca-Fontán; Marta Rivero; Teresa Cavero; Montserrat Díaz-Encarnación; Virginia Cabello; Gema Ariceta; Luis F Quintana; Helena Marco; Xoana Barros; Natalia Ramos; Nuria Rodríguez-Mendiola; Sonia Cruz; Gema Fernández-Juárez; Adela Rodríguez; Ana Pérez de José; Cristina Rabasco; Raquel Rodado; Loreto Fernández; Vanessa Pérez-Gómez; Ana Ávila; Luis Bravo; Natalia Espinosa; Natalia Allende; Maria Dolores Sanchez de la Nieta; Eva Rodríguez; Teresa Olea; Marta Melgosa; Ana Huerta; Rosa Miquel; Carmen Mon; Gloria Fraga; Alberto de Lorenzo; Juliana Draibe; Fayna González; Amir Shabaka; Maria Esperanza López-Rubio; María Ángeles Fenollosa; Luis Martín-Penagos; Iara Da Silva; Juana Alonso Titos; Santiago Rodríguez de Córdoba; Elena Goicoechea de Jorge; Manuel Praga Journal: Clin Kidney J Date: 2022-04-28