@article{3105503,
    title = "Histological grading in primary membranous nephropathy is essential for clinical management and predicts outcome of patients",
    author = "Stangou, M.J. and Marinaki, S. and Papachristou, E. and Liapis, G. and Pateinakis, P. and Gakiopoulou, H. and Nikolaidou, C. and Kolovou, K. and Lampropoulou, I.-T. and Zerbala, S. and Papadea, P. and Dounousi, E. and Balafa, O. and Pavlakou, P. and Andrikos, A. and Balassi, E. and Manolakaki, P. and Moustakas, G. and Galitsiou, D. and Mitsopoulos, E. and Vourlakou, C. and Choulitoudi, V. and Andronikidi, P.-E. and Stefanidis, I. and Golfinopoulos, S. and Dafnis, E. and Stylianou, K. and Panagoutsos, S. and Papadogianakis, A. and Tzanakis, I. and Sioulis, A. and Vlahakos, D. and Grapsa, I. and Tsilivigkou, M. and Kaperonis, N. and Paliouras, C. and Dioudis, C. and Spaia, S. and Apostolou, T. and Iatrou, C. and Boletis, J. and Goumenos, D. and Papagianni, A.",
    journal = "Diagnostic Histopathology",
    year = "2019",
    volume = "75",
    number = "5",
    pages = "660-671",
    publisher = "Wiley-Blackwell Publishing Ltd",
    issn = "1756-2317",
    doi = "10.1111/his.13955",
    keywords = "immunosuppressive agent, adolescent;  adult;  aged;  Article;  atrophy;  clinical evaluation;  clinical outcome;  cohort analysis;  disease association;  disease severity;  end stage renal disease;  estimated glomerular filtration rate;  female;  focal glomerulosclerosis;  follow up;  hemodialysis;  histopathology;  human;  human tissue;  hyaline degeneration;  immunosuppressive treatment;  kidney fibrosis;  kidney function;  kidney injury;  major clinical study;  male;  membranous glomerulonephritis;  nephrotic syndrome;  predictive value;  priority journal;  prognosis;  proteinuria;  treatment response;  tubular atrophy;  vascular disease;  vascular hyalinosis;  biopsy;  cytochemistry;  kidney;  kidney disease;  membranous glomerulonephritis;  middle aged;  pathology;  prognosis;  retrospective study;  very elderly;  young adult, Adolescent;  Adult;  Aged;  Aged, 80 and over;  Biopsy;  Female;  Glomerulonephritis, Membranous;  Histocytochemistry;  Humans;  Immunosuppressive Agents;  Kidney;  Kidney Diseases;  Male;  Middle Aged;  Prognosis;  Retrospective Studies;  Young Adult",
    abstract = "Aims: Diagnosis of primary membranous nephropathy (PMN) is mainly based on immunofluorescence/immunohistochemistry findings. However, assessment of specific features on optical microscopy can help to estimate the severity of the disease, guide treatment and predict the response. The aim of this study was to identify, classify and grade the precise histological findings in PMN to predict renal function outcome and guide treatment. Methods and results: Histological parameters, including focal segmental sclerosis (FSGS), tubular atrophy (TA), interstitial fibrosis (IF) and vascular hyalinosis (VH), were re-evaluated in 752 patients with PMN. Their predictive value was estimated separately, and also in a combination score (FSTIV) graded from 0 to 4. Finally, the impact of histology was assessed in the response to immunosuppressive treatment. Mean age of patients was 53.3 (15–85) years and most presented with nephrotic syndrome. FSGS was present in 32% and VH in 51% of the patients, while TA and IF were graded as stage ≥1 in 52% and 51.4%, respectively. The follow-up period was 122.3 (112–376) months. FSGS, TA and IF and VH were associated with impaired renal function at diagnosis (P = 0.02, P < 0.0001, P = 0.001 and P = 0.02, respectively) and at the end of follow-up (P = 0.004, P < 0.0001, P < 0.0001 and P = 0.04, respectively). In multiple regression and binary logistic analysis, the presence of FSGS and degree of TA were the most significant parameters predicting renal function outcome, defined either by eGFR (end), FSGS (r = 0.6, P < 0.0001) and TA (r = 0.6, P < 0.0001), or by the endpoint of >50% eGFR reduction, FSGS (P = 0.001) and TA (P = 0.02). Also, patients presented with FSGS, IF, VH and/or with FSTIV > 1 could benefit from immunosuppression, regardless of clinical presentation. Conclusions: The presence and degree of four histological indices, FSGS, VH, TA and IF, assessed separately or in combination, and FSTIV score not only predict renal function outcome after long-term follow-up, but can also help in the choice of appropriate treatment. Decisions concerning immunosuppressive treatment can be guided by pathology regardless of clinical findings. © 2019 The Authors. Histopathology published by John Wiley & Sons Ltd"
}