title: Evidence from the Oxford Classification cohort supports the clinical value of subclassification of focal segmental glomerulosclerosis in IgA nephropathy.
abstract: Focal segmental glomerulosclerosis (FSGS) is a common finding in IgA nephropathy (IgAN). Here we assessed FSGS lesions in the Oxford Classification patient cohort and correlated histology with clinical presentation and outcome to determine whether subclassification of the S score in IgAN is reproducible and of clinical value. Our subclassification of lesions in 137 individuals with segmental glomerulosclerosis or adhesion (S1) identified 38% with podocyte hypertrophy, 10% with hyalinosis, 9% with resorption droplets within podocytes, 7% with tip lesions, 3% with perihilar sclerosis, and 2% with endocapillary foam cells. Reproducibility was good or excellent for tip lesions, hyalinosis, and perihilar sclerosis; moderate for podocyte hypertrophy; and poor for resorption droplets, adhesion only, and endocapillary foam cells. Podocyte hypertrophy and tip lesions were strongly associated with greater initial proteinuria. During follow-up of patients without immunosuppression, those with these features had more rapid renal function decline and worse survival from a combined event compared to S1 patients without such features and those without FSGS. Also in individuals with podocyte hypertrophy or tip lesions, immunosuppressive therapy was associated with better renal survival. In IgA nephropathy, the presence of podocyte hypertrophy or tip lesions, markers of podocyte injury, were reproducible. These features are strongly associated with proteinuria and, in untreated patients, carry a worse prognosis. Thus, our findings support reporting podocytopathic features alongside the S score of the Oxford Classification.
authors.affiliation: Department of Cellular Pathology, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: Shubha S
authors.initials: SS
authors.lastname: Bellur
authors.affiliation: Division of Nephrology, Hôpital du Sacré-Coeur de Montréal, Montreal, Quebec, Canada.
authors.forename: Fanny
authors.initials: F
authors.lastname: Lepeytre
authors.affiliation: Department of Cellular Pathology, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: Olga
authors.initials: O
authors.lastname: Vorobyeva
authors.affiliation: Division of Nephrology, Hôpital du Sacré-Coeur de Montréal, Montreal, Quebec, Canada.
authors.forename: Stéphan
authors.initials: S
authors.lastname: Troyanov
authors.affiliation: Department of Medicine, Imperial College, London, United Kingdom.
authors.forename: H Terence
authors.initials: HT
authors.lastname: Cook
authors.affiliation: Department of Cellular Pathology, John Radcliffe Hospital, Oxford, United Kingdom. Electronic address: ian.roberts@ouh.nhs.uk.
authors.forename: Ian S D
authors.initials: IS
authors.lastname: Roberts
mesh_terms: D000293:Adolescent; D000328:Adult; D001706:Biopsy; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D005922:Glomerulonephritis, IGA / Q000150:complications / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D005923:Glomerulosclerosis, Focal Segmental / Q000145:classification* / Q000150:complications / Q000401:mortality / Q000473:pathology; D006801:Humans; D006984:Hypertrophy / Q000175:diagnosis; D007165:Immunosuppression Therapy; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D050199:Podocytes / Q000473:pathology*; D011379:Prognosis; D011507:Proteinuria / Q000652:urine*; D015203:Reproducibility of Results; D012189:Retrospective Studies; D055815:Young Adult
keywords: IgA nephropathy; podocytopathy; segmental sclerosis