Evidence from the large VALIGA cohort validates the subclassification of focal segmental glomerulosclerosis in IgA nephropathy
Evidence from the Oxford IgA nephropathy (IgAN) cohort supports the clinical value of subclassifying focal segmental glomerulosclerosis lesions (S1). Using the larger Validation in IgA (VALIGA) study cohort, we investigated the association between podocytopathic changes and higher proteinuria, kidne...
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| Veröffentlicht in: | Kidney international 2024-06, Vol.105 (6), p.1279-1290 |
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| creator | Bellur, Shubha S. Vorobyeva, Olga Coppo, Rosanna Coppo, R. Feehaly, J. Cook, H.T. Roberts, I. Maixnerova, D. Lundberg, S. Emma, F. Fuiano, L. Beltrame, G. Rollino, C. Amore, A. Camilla, R. Peruzzi, L. Praga, M. Feriozzi, S. Polci, R. Segoloni, G. Colla, L. Pani, A. Piras, D. Angioi, A. Cancarini, G. Ravera, S. Durlik, M. Di Giulio, S. Pugliese, F. Serriello, I. Caliskan, Y. Kilicaslan, I. Locatelli, F. Del Vecchio, L. Wetzels, J.F.M. Berg, U. da Costa Ferreira, A.C. Maggio, M. Magistroni, R. Topaloglu, R. D’Amico, M. Papagianni, K. Stangou, M. Goumenos, D. Papasotirious, M. Gerolymos, M. Galesic, K. Toric, L. Geddes, C. Siamopoulos, K. Stratta, P. Quaglia, M. Bergia, R. Cravero, R. Fellstrom, B. Kloster Smerud, H. Ferrario, F. Egido, J. Martin, C. Eitner, F. Bernich, P. Menè, P. Morosetti, M. Boria Grinyo, J.M. Cusinato, S. Benozzi, L. Savoldi, S. Licata, C. Hryszko, T. Klinger, M. Kamińska, D. Krajewska, M. Mariano, F. Pozzi, C. Boero, R. Cambier, A. Bellur, S. Mazzucco, G. Honsova, E. Sundelin, B. Di Palma, A.M. Asunis, A.M. Barratt, J. Arce Terroba, J. Fortunato, M. Pantzaki, A. Ozluk, Y. Steenbergen, E. Riispere, Z. Kipgen, D. Galesic Ljubanovic, D. Gakiopoulou, H. Cannata Ortiz, P. Groene, H.J. Stoppacciaro, A. Bruijn, J. Fulladosa Oliveras, X. Maldyk, J. Ioachim, E. Royal, V. |
| description | Evidence from the Oxford IgA nephropathy (IgAN) cohort supports the clinical value of subclassifying focal segmental glomerulosclerosis lesions (S1). Using the larger Validation in IgA (VALIGA) study cohort, we investigated the association between podocytopathic changes and higher proteinuria, kidney outcome and response to immunosuppressive therapy. All biopsies were evaluated for glomeruli with segmental capillary occlusion by matrix (“not otherwise specified”, NOS lesion), simple capsular adhesion without capillary occlusion (Adh), tip lesions, and podocyte hypertrophy (PH). S1 required a NOS lesion and/or Adh. A Chi-Squared Automatic Interaction Detection method was used to identify subgroups of FSGS lesions associated with distinctive proteinuria at biopsy. We assessed survival from a combined event (kidney failure or 50% decline in estimated glomerular filtration rate). Finally, we evaluated within each subgroup if immunosuppression was associated with a favorable outcome using propensity analysis. In 1147 patients, S1 was found in 70% of biopsies. Subclassification found NOS lesions in 44%, Adh in 59%, PH in 13%, and tip lesions in 3%, with much overlap. Four subgroups were identified with progressively higher proteinuria: from lowest, S1 without NOS, S1 with NOS but without Adh/PH, to highest, S1 with NOS and Adh but without PH, and S1 with NOS and PH. These four subgroups showed progressively worse kidney survival. Immunosuppression was associated with a better outcome only in the two highest proteinuria subgroups. Propensity analysis in these two groups, adjusted for clinical and pathological findings, found a significantly reduced time-dependent hazard of combined outcome with corticosteroids. Podocyte hypertrophy and glomeruli with simple adhesions appeared to reflect active lesions associated with a response to corticosteroids, while other S1 lesions defined chronicity. Thus, our findings support subclassifying S1 lesions in IgAN.
[Display omitted] |
| doi_str_mv | 10.1016/j.kint.2024.03.011 |
| format | Article |
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Using the larger Validation in IgA (VALIGA) study cohort, we investigated the association between podocytopathic changes and higher proteinuria, kidney outcome and response to immunosuppressive therapy. All biopsies were evaluated for glomeruli with segmental capillary occlusion by matrix (“not otherwise specified”, NOS lesion), simple capsular adhesion without capillary occlusion (Adh), tip lesions, and podocyte hypertrophy (PH). S1 required a NOS lesion and/or Adh. A Chi-Squared Automatic Interaction Detection method was used to identify subgroups of FSGS lesions associated with distinctive proteinuria at biopsy. We assessed survival from a combined event (kidney failure or 50% decline in estimated glomerular filtration rate). Finally, we evaluated within each subgroup if immunosuppression was associated with a favorable outcome using propensity analysis. In 1147 patients, S1 was found in 70% of biopsies. Subclassification found NOS lesions in 44%, Adh in 59%, PH in 13%, and tip lesions in 3%, with much overlap. Four subgroups were identified with progressively higher proteinuria: from lowest, S1 without NOS, S1 with NOS but without Adh/PH, to highest, S1 with NOS and Adh but without PH, and S1 with NOS and PH. These four subgroups showed progressively worse kidney survival. Immunosuppression was associated with a better outcome only in the two highest proteinuria subgroups. Propensity analysis in these two groups, adjusted for clinical and pathological findings, found a significantly reduced time-dependent hazard of combined outcome with corticosteroids. Podocyte hypertrophy and glomeruli with simple adhesions appeared to reflect active lesions associated with a response to corticosteroids, while other S1 lesions defined chronicity. Thus, our findings support subclassifying S1 lesions in IgAN.
[Display omitted]</description><identifier>ISSN: 0085-2538</identifier><identifier>ISSN: 1523-1755</identifier><identifier>EISSN: 1523-1755</identifier><identifier>DOI: 10.1016/j.kint.2024.03.011</identifier><identifier>PMID: 38554992</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>IgA nephropathy ; podocytopathy ; segmental sclerosis ; subclassification</subject><ispartof>Kidney international, 2024-06, Vol.105 (6), p.1279-1290</ispartof><rights>2024 International Society of Nephrology</rights><rights>Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. 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D.</creatorcontrib><creatorcontrib>Krajewska, M.</creatorcontrib><creatorcontrib>Mariano, F.</creatorcontrib><creatorcontrib>Pozzi, C.</creatorcontrib><creatorcontrib>Boero, R.</creatorcontrib><creatorcontrib>Cambier, A.</creatorcontrib><creatorcontrib>Bellur, S.</creatorcontrib><creatorcontrib>Mazzucco, G.</creatorcontrib><creatorcontrib>Honsova, E.</creatorcontrib><creatorcontrib>Sundelin, B.</creatorcontrib><creatorcontrib>Di Palma, A.M.</creatorcontrib><creatorcontrib>Asunis, A.M.</creatorcontrib><creatorcontrib>Barratt, J.</creatorcontrib><creatorcontrib>Arce Terroba, J.</creatorcontrib><creatorcontrib>Fortunato, M.</creatorcontrib><creatorcontrib>Pantzaki, A.</creatorcontrib><creatorcontrib>Ozluk, Y.</creatorcontrib><creatorcontrib>Steenbergen, E.</creatorcontrib><creatorcontrib>Riispere, Z.</creatorcontrib><creatorcontrib>Kipgen, D.</creatorcontrib><creatorcontrib>Galesic Ljubanovic, D.</creatorcontrib><creatorcontrib>Gakiopoulou, H.</creatorcontrib><creatorcontrib>Cannata Ortiz, P.</creatorcontrib><creatorcontrib>Groene, H.J.</creatorcontrib><creatorcontrib>Stoppacciaro, A.</creatorcontrib><creatorcontrib>Bruijn, J.</creatorcontrib><creatorcontrib>Fulladosa Oliveras, X.</creatorcontrib><creatorcontrib>Maldyk, J.</creatorcontrib><creatorcontrib>Ioachim, E.</creatorcontrib><creatorcontrib>Royal, V.</creatorcontrib><creatorcontrib>Validation in IgA Nephropathy study group</creatorcontrib><title>Evidence from the large VALIGA cohort validates the subclassification of focal segmental glomerulosclerosis in IgA nephropathy</title><title>Kidney international</title><addtitle>Kidney Int</addtitle><description>Evidence from the Oxford IgA nephropathy (IgAN) cohort supports the clinical value of subclassifying focal segmental glomerulosclerosis lesions (S1). Using the larger Validation in IgA (VALIGA) study cohort, we investigated the association between podocytopathic changes and higher proteinuria, kidney outcome and response to immunosuppressive therapy. All biopsies were evaluated for glomeruli with segmental capillary occlusion by matrix (“not otherwise specified”, NOS lesion), simple capsular adhesion without capillary occlusion (Adh), tip lesions, and podocyte hypertrophy (PH). S1 required a NOS lesion and/or Adh. A Chi-Squared Automatic Interaction Detection method was used to identify subgroups of FSGS lesions associated with distinctive proteinuria at biopsy. We assessed survival from a combined event (kidney failure or 50% decline in estimated glomerular filtration rate). Finally, we evaluated within each subgroup if immunosuppression was associated with a favorable outcome using propensity analysis. In 1147 patients, S1 was found in 70% of biopsies. Subclassification found NOS lesions in 44%, Adh in 59%, PH in 13%, and tip lesions in 3%, with much overlap. Four subgroups were identified with progressively higher proteinuria: from lowest, S1 without NOS, S1 with NOS but without Adh/PH, to highest, S1 with NOS and Adh but without PH, and S1 with NOS and PH. These four subgroups showed progressively worse kidney survival. Immunosuppression was associated with a better outcome only in the two highest proteinuria subgroups. Propensity analysis in these two groups, adjusted for clinical and pathological findings, found a significantly reduced time-dependent hazard of combined outcome with corticosteroids. Podocyte hypertrophy and glomeruli with simple adhesions appeared to reflect active lesions associated with a response to corticosteroids, while other S1 lesions defined chronicity. Thus, our findings support subclassifying S1 lesions in IgAN.
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X.</creator><creator>Maldyk, J.</creator><creator>Ioachim, E.</creator><creator>Royal, V.</creator><general>Elsevier Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-4713-6282</orcidid><orcidid>https://orcid.org/0009-0006-4475-181X</orcidid></search><sort><creationdate>20240601</creationdate><title>Evidence from the large VALIGA cohort validates the subclassification of focal segmental glomerulosclerosis in IgA nephropathy</title><author>Bellur, Shubha S. ; Vorobyeva, Olga ; Coppo, Rosanna ; Coppo, R. ; Feehaly, J. ; Cook, H.T. ; Roberts, I. ; Maixnerova, D. ; Lundberg, S. ; Emma, F. ; Fuiano, L. ; Beltrame, G. ; Rollino, C. ; Amore, A. ; Camilla, R. ; Peruzzi, L. ; Praga, M. ; Feriozzi, S. ; Polci, R. ; Segoloni, G. ; Colla, L. ; Pani, A. ; Piras, D. ; Angioi, A. ; Cancarini, G. ; Ravera, S. ; Durlik, M. ; Di Giulio, S. ; Pugliese, F. ; Serriello, I. ; Caliskan, Y. ; Kilicaslan, I. ; Locatelli, F. ; Del Vecchio, L. ; Wetzels, J.F.M. ; Berg, U. ; da Costa Ferreira, A.C. ; Maggio, M. ; Magistroni, R. ; Topaloglu, R. ; D’Amico, M. ; Papagianni, K. ; Stangou, M. ; Goumenos, D. ; Papasotirious, M. ; Gerolymos, M. ; Galesic, K. ; Toric, L. ; Geddes, C. ; Siamopoulos, K. ; Stratta, P. ; Quaglia, M. ; Bergia, R. ; Cravero, R. ; Fellstrom, B. ; Kloster Smerud, H. ; Ferrario, F. ; Egido, J. ; Martin, C. ; Eitner, F. ; Bernich, P. ; Menè, P. ; Morosetti, M. ; Boria Grinyo, J.M. ; Cusinato, S. ; Benozzi, L. ; Savoldi, S. ; Licata, C. ; Hryszko, T. ; Klinger, M. ; Kamińska, D. ; Krajewska, M. ; Mariano, F. ; Pozzi, C. ; Boero, R. ; Cambier, A. ; Bellur, S. ; Mazzucco, G. ; Honsova, E. ; Sundelin, B. ; Di Palma, A.M. ; Asunis, A.M. ; Barratt, J. ; Arce Terroba, J. ; Fortunato, M. ; Pantzaki, A. ; Ozluk, Y. ; Steenbergen, E. ; Riispere, Z. ; Kipgen, D. ; Galesic Ljubanovic, D. ; Gakiopoulou, H. ; Cannata Ortiz, P. ; Groene, H.J. ; Stoppacciaro, A. ; Bruijn, J. ; Fulladosa Oliveras, X. ; Maldyk, J. ; Ioachim, E. ; Royal, V.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-9ebb4f3fef2a74f908a7ed56b6c1954f2af67ee66b954bcd73b2c79ead3e0d993</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>IgA nephropathy</topic><topic>podocytopathy</topic><topic>segmental sclerosis</topic><topic>subclassification</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bellur, Shubha S.</creatorcontrib><creatorcontrib>Vorobyeva, Olga</creatorcontrib><creatorcontrib>Coppo, Rosanna</creatorcontrib><creatorcontrib>Coppo, R.</creatorcontrib><creatorcontrib>Feehaly, J.</creatorcontrib><creatorcontrib>Cook, H.T.</creatorcontrib><creatorcontrib>Roberts, I.</creatorcontrib><creatorcontrib>Maixnerova, D.</creatorcontrib><creatorcontrib>Lundberg, S.</creatorcontrib><creatorcontrib>Emma, F.</creatorcontrib><creatorcontrib>Fuiano, L.</creatorcontrib><creatorcontrib>Beltrame, G.</creatorcontrib><creatorcontrib>Rollino, C.</creatorcontrib><creatorcontrib>Amore, A.</creatorcontrib><creatorcontrib>Camilla, R.</creatorcontrib><creatorcontrib>Peruzzi, L.</creatorcontrib><creatorcontrib>Praga, M.</creatorcontrib><creatorcontrib>Feriozzi, S.</creatorcontrib><creatorcontrib>Polci, R.</creatorcontrib><creatorcontrib>Segoloni, G.</creatorcontrib><creatorcontrib>Colla, L.</creatorcontrib><creatorcontrib>Pani, A.</creatorcontrib><creatorcontrib>Piras, D.</creatorcontrib><creatorcontrib>Angioi, A.</creatorcontrib><creatorcontrib>Cancarini, G.</creatorcontrib><creatorcontrib>Ravera, S.</creatorcontrib><creatorcontrib>Durlik, M.</creatorcontrib><creatorcontrib>Di Giulio, S.</creatorcontrib><creatorcontrib>Pugliese, F.</creatorcontrib><creatorcontrib>Serriello, I.</creatorcontrib><creatorcontrib>Caliskan, Y.</creatorcontrib><creatorcontrib>Kilicaslan, I.</creatorcontrib><creatorcontrib>Locatelli, 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A.</creatorcontrib><creatorcontrib>Bellur, S.</creatorcontrib><creatorcontrib>Mazzucco, G.</creatorcontrib><creatorcontrib>Honsova, E.</creatorcontrib><creatorcontrib>Sundelin, B.</creatorcontrib><creatorcontrib>Di Palma, A.M.</creatorcontrib><creatorcontrib>Asunis, A.M.</creatorcontrib><creatorcontrib>Barratt, J.</creatorcontrib><creatorcontrib>Arce Terroba, J.</creatorcontrib><creatorcontrib>Fortunato, M.</creatorcontrib><creatorcontrib>Pantzaki, A.</creatorcontrib><creatorcontrib>Ozluk, Y.</creatorcontrib><creatorcontrib>Steenbergen, E.</creatorcontrib><creatorcontrib>Riispere, Z.</creatorcontrib><creatorcontrib>Kipgen, D.</creatorcontrib><creatorcontrib>Galesic Ljubanovic, D.</creatorcontrib><creatorcontrib>Gakiopoulou, H.</creatorcontrib><creatorcontrib>Cannata Ortiz, P.</creatorcontrib><creatorcontrib>Groene, H.J.</creatorcontrib><creatorcontrib>Stoppacciaro, A.</creatorcontrib><creatorcontrib>Bruijn, J.</creatorcontrib><creatorcontrib>Fulladosa Oliveras, X.</creatorcontrib><creatorcontrib>Maldyk, J.</creatorcontrib><creatorcontrib>Ioachim, E.</creatorcontrib><creatorcontrib>Royal, V.</creatorcontrib><creatorcontrib>Validation in IgA Nephropathy study group</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Kidney international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bellur, Shubha S.</au><au>Vorobyeva, Olga</au><au>Coppo, Rosanna</au><au>Coppo, R.</au><au>Feehaly, J.</au><au>Cook, H.T.</au><au>Roberts, I.</au><au>Maixnerova, D.</au><au>Lundberg, S.</au><au>Emma, F.</au><au>Fuiano, L.</au><au>Beltrame, G.</au><au>Rollino, C.</au><au>Amore, A.</au><au>Camilla, R.</au><au>Peruzzi, L.</au><au>Praga, M.</au><au>Feriozzi, S.</au><au>Polci, R.</au><au>Segoloni, G.</au><au>Colla, L.</au><au>Pani, A.</au><au>Piras, D.</au><au>Angioi, A.</au><au>Cancarini, G.</au><au>Ravera, S.</au><au>Durlik, M.</au><au>Di Giulio, S.</au><au>Pugliese, F.</au><au>Serriello, I.</au><au>Caliskan, Y.</au><au>Kilicaslan, I.</au><au>Locatelli, F.</au><au>Del Vecchio, L.</au><au>Wetzels, J.F.M.</au><au>Berg, U.</au><au>da Costa Ferreira, A.C.</au><au>Maggio, M.</au><au>Magistroni, R.</au><au>Topaloglu, R.</au><au>D’Amico, M.</au><au>Papagianni, K.</au><au>Stangou, M.</au><au>Goumenos, D.</au><au>Papasotirious, M.</au><au>Gerolymos, M.</au><au>Galesic, K.</au><au>Toric, L.</au><au>Geddes, C.</au><au>Siamopoulos, K.</au><au>Stratta, P.</au><au>Quaglia, M.</au><au>Bergia, R.</au><au>Cravero, R.</au><au>Fellstrom, B.</au><au>Kloster Smerud, H.</au><au>Ferrario, F.</au><au>Egido, J.</au><au>Martin, C.</au><au>Eitner, F.</au><au>Bernich, P.</au><au>Menè, P.</au><au>Morosetti, M.</au><au>Boria Grinyo, J.M.</au><au>Cusinato, S.</au><au>Benozzi, L.</au><au>Savoldi, S.</au><au>Licata, C.</au><au>Hryszko, T.</au><au>Klinger, M.</au><au>Kamińska, D.</au><au>Krajewska, M.</au><au>Mariano, F.</au><au>Pozzi, C.</au><au>Boero, R.</au><au>Cambier, A.</au><au>Bellur, S.</au><au>Mazzucco, G.</au><au>Honsova, E.</au><au>Sundelin, B.</au><au>Di Palma, A.M.</au><au>Asunis, A.M.</au><au>Barratt, J.</au><au>Arce Terroba, J.</au><au>Fortunato, M.</au><au>Pantzaki, A.</au><au>Ozluk, Y.</au><au>Steenbergen, E.</au><au>Riispere, Z.</au><au>Kipgen, D.</au><au>Galesic Ljubanovic, D.</au><au>Gakiopoulou, H.</au><au>Cannata Ortiz, P.</au><au>Groene, H.J.</au><au>Stoppacciaro, A.</au><au>Bruijn, J.</au><au>Fulladosa Oliveras, X.</au><au>Maldyk, J.</au><au>Ioachim, E.</au><au>Royal, V.</au><aucorp>Validation in IgA Nephropathy study group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evidence from the large VALIGA cohort validates the subclassification of focal segmental glomerulosclerosis in IgA nephropathy</atitle><jtitle>Kidney international</jtitle><addtitle>Kidney Int</addtitle><date>2024-06-01</date><risdate>2024</risdate><volume>105</volume><issue>6</issue><spage>1279</spage><epage>1290</epage><pages>1279-1290</pages><issn>0085-2538</issn><issn>1523-1755</issn><eissn>1523-1755</eissn><abstract>Evidence from the Oxford IgA nephropathy (IgAN) cohort supports the clinical value of subclassifying focal segmental glomerulosclerosis lesions (S1). Using the larger Validation in IgA (VALIGA) study cohort, we investigated the association between podocytopathic changes and higher proteinuria, kidney outcome and response to immunosuppressive therapy. All biopsies were evaluated for glomeruli with segmental capillary occlusion by matrix (“not otherwise specified”, NOS lesion), simple capsular adhesion without capillary occlusion (Adh), tip lesions, and podocyte hypertrophy (PH). S1 required a NOS lesion and/or Adh. A Chi-Squared Automatic Interaction Detection method was used to identify subgroups of FSGS lesions associated with distinctive proteinuria at biopsy. We assessed survival from a combined event (kidney failure or 50% decline in estimated glomerular filtration rate). Finally, we evaluated within each subgroup if immunosuppression was associated with a favorable outcome using propensity analysis. In 1147 patients, S1 was found in 70% of biopsies. Subclassification found NOS lesions in 44%, Adh in 59%, PH in 13%, and tip lesions in 3%, with much overlap. Four subgroups were identified with progressively higher proteinuria: from lowest, S1 without NOS, S1 with NOS but without Adh/PH, to highest, S1 with NOS and Adh but without PH, and S1 with NOS and PH. These four subgroups showed progressively worse kidney survival. Immunosuppression was associated with a better outcome only in the two highest proteinuria subgroups. Propensity analysis in these two groups, adjusted for clinical and pathological findings, found a significantly reduced time-dependent hazard of combined outcome with corticosteroids. Podocyte hypertrophy and glomeruli with simple adhesions appeared to reflect active lesions associated with a response to corticosteroids, while other S1 lesions defined chronicity. Thus, our findings support subclassifying S1 lesions in IgAN.
[Display omitted]</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>38554992</pmid><doi>10.1016/j.kint.2024.03.011</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0003-4713-6282</orcidid><orcidid>https://orcid.org/0009-0006-4475-181X</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0085-2538 |
| ispartof | Kidney international, 2024-06, Vol.105 (6), p.1279-1290 |
| issn | 0085-2538 1523-1755 1523-1755 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_3022571388 |
| source | Alma/SFX Local Collection |
| subjects | IgA nephropathy podocytopathy segmental sclerosis subclassification |
| title | Evidence from the large VALIGA cohort validates the subclassification of focal segmental glomerulosclerosis in IgA nephropathy |
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