Is there long-term value of pathology scoring in immunoglobulin A nephropathy? A validation study of the Oxford Classification for IgA Nephropathy (VALIGA) update
Authors: Coppo Rosanna , D'Arrigo Graziella , Tripepi Giovanni , Russo Maria Luisa , Roberts Ian S D , Bellur Shubha , Cattran Daniel , Cook Terence H , Feehally John , Tesar Vladimir , Maixnerova Dita , Peruzzi Licia , Amore Alessandro , Lundberg Sigrid , Di Palma Anna Maria , Gesualdo Loreto , Emma Francesco , Rollino Cristiana , Praga Manuel , Biancone Luigi , Pani Antonello , Feriozzi Sandro , Polci Rosaria , Barratt Jonathan , Del Vecchio Lucia , Locatelli Francesco , Pierucci Alessandro , Caliskan Yasar , Perkowska-Ptasinska Agnieszka , Durlik Magdalena , Moggia Elisabetta , Ballarin José C , Wetzels Jack F M , Goumenos Dimitris , Papasotiriou Marios , Galesic Kresimir , Toric Luka , Papagianni Aikaterini , Stangou Maria , Benozzi Luisa , Cusinato Stefano , Berg Ulla , Topaloglu Rezan , Maggio Milena , Ots-Rosenberg Mai , D’Amico Marco , Geddes Colin , Balafa Olga , Quaglia Marco , Cravero Raffaella , Lino Cirami Calogero , Fellstrom Bengt , Floege Jürgen , Egido Jesus , Mallamaci Francesca , Zoccali Carmine ,   for the ERA-EDTA Immunonephrology Working Group, Tesar V , Maixnerova D , Lundberg S , Gesualdo L , Emma F , Fuiano L , Beltrame G , Rollino C , Coppo R , Amore A , Camilla R , Peruzzi L , Praga M , Feriozzi S , Polci R , Segoloni G , Colla L , Pani A , Angioi A , Piras L , Feehally J , Cancarini G , Ravera S , Durlik M , Moggia E , Ballarin J , Di Giulio S , Pugliese F , Serriello I , Caliskan Y , Sever M , Kilicaslan I , Locatelli F , Del Vecchio L , Wetzels J F M , Peters H , Berg U , Carvalho F , da Costa Ferreira A C , Maggio M , Wiecek A , Ots-Rosenberg M , Magistroni R , Topaloglu R , Bilginer Y , D’Amico M , Stangou M , Giacchino F , Goumenos D , Papastirou M , Galesic K , Toric L , Geddes C , Siamopoulos K , Balafa O , Galliani M , Stratta P , Quaglia M , Bergia R , Cravero R , Salvadori M , Cirami L , Fellstrom B , Kloster Smerud H , Ferrario F , Stellato T , Egido J , Martin C , Floege J , Eitner F , Rauen T , Lupo A , Bernich P , Menè P , Morosetti M , van Kooten C , Rabelink T , Reinders M E J , Boria Grinyo J M , Cusinato S , Benozzi L , Savoldi S , Licata C , Mizerska-Wasiak M , Roszkowska-Blaim M , Martina G , Messuerotti A , Dal Canton A , Esposito C , Migotto C , Triolo G , Mariano F , Pozzi C , Boero R , Mazzucco G , Giannakakis C , Honsova E , Sundelin B , Di Palma A M , Ferrario F , Gutiérrez E , Asunis A M , Barratt J , Tardanico R , Perkowska-Ptasinska A , Arce Terroba J , Fortunato M , Pantzaki A , Ozluk Y , Steenbergen E , Soderberg M , Riispere Z , Furci L , Orhan D , Kipgen D , Casartelli D , GalesicLjubanovic D , Gakiopoulou H , Bertoni E , Cannata Ortiz P , Karkoszka H , Groene H J , Stoppacciaro A , Bajema I , Bruijn J , Fulladosa Oliveras X , Maldyk J , Ioachim E 
Published: September 2018

Abstract

Background
It is unknown whether renal pathology lesions in immunoglobulin A nephropathy (IgAN) correlate with renal outcomes over decades of follow-up.

Methods
In 1130 patients of the original Validation Study of the Oxford Classification for IgA Nephropathy (VALIGA) cohort, we studied the relationship between the MEST score (mesangial hypercellularity, M; endocapillary hypercellularity, E; segmental glomerulosclerosis, S; tubular atrophy/interstitial fibrosis, T), crescents (C) and other histological lesions with both a combined renal endpoint [50% estimated glomerular filtration rate (eGFR) loss or kidney failure] and the rate of eGFR decline over a follow-up period extending to 35 years [median 7 years (interquartile range 4.1–10.8)].

Results
In this extended analysis, M1, S1 and T1–T2 lesions as well as the whole MEST score were independently related with the combined endpoint (P &lt; 0.01), and there was no effect modification by age for these associations, suggesting that they may be valid in children and in adults as well. Only T lesions were associated with the rate of eGFR loss in the whole cohort, whereas C showed this association only in patients not treated with immunosuppression. In separate prognostic analyses, the whole set of pathology lesions provided a gain in discrimination power over the clinical variables alone, which was similar at 5 years (+2.0%) and for the whole follow-up (+1.8%). A similar benefit was observed for risk reclassification analyses (+2.7% and +2.4%).

Conclusion
Long-term follow-up analyses of the VALIGA cohort showed that the independent relationship between kidney biopsy findings and the risk of progression towards kidney failure in IgAN remains unchanged across all age groups and decades after the renal biopsy.