Histopathological predictors of renal outcomes in idiopathic membranous nephropathy with a focus on global sclerotic glomeruli ratio

Abstract Idiopathic membranous nephropathy (MN) shows variable renal outcomes, and reliable histologic markers for risk stratification are limited. The global sclerotic glomeruli ratio (GSGR) may reflect chronic kidney damage and help predict progression, but its prognostic value and optimal threshold remain unclear. We retrospectively analyzed 322 patients with biopsy-proven idiopathic MN from the Turkish Society of Nephrology-Glomerular Diseases Study Group registry, excluding those with an estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m² at diagnosis or insufficient data. GSGR was calculated as the percentage of globally sclerotic glomeruli among total glomeruli. Histopathological parameters, including exudative glomerular changes, tubular atrophy/interstitial fibrosis (TA/IF), and vascular alterations, were semi-quantitatively graded according to the Renal Pathology Atlas (Fogo, 2022). Specifically, TA/IF was graded as: Grade 0 (< 5%), Grade 1 (5–25%), Grade 2 26–50%, and Grade 3 (> 50%) of cortical area involvement. Exudative changes were defined as intracapillary leukocyte accumulation and hyaline deposits in ≥ 25% of non-sclerotic glomeruli. The primary composite outcome was ≥ 50% eGFR decline from baseline, progression to eGFR < 15 mL/min/1.73 m², dialysis initiation, or kidney transplantation. Median follow-up was 60 months (IQR 48–72). Thirty patients (9.3%) reached the composite outcome. Receiver operating characteristic analysis identified a GSGR threshold of 15.7% (AUC 0.956; sensitivity 93.3%; specificity 82.7%). Patients with GSGR ≥ 15.7% had significantly higher event rates (35.1% vs. 1.2%; p < 0.001). In multivariate analysis, high GSGR, exudative changes, and response to immunosuppressive therapy independently predicted adverse outcomes. These associations remained significant across treatment subgroups. Sensitivity analyses confirmed these associations across multiple model specifications. Anti-PLA2R positivity correlated with higher baseline proteinuria but not independently with renal outcomes. A GSGR ≥ 15.7% is a strong, independent predictor of renal progression in idiopathic MN. Incorporating GSGR and exudative changes into risk stratification may improve prognostic assessment and therapeutic decision-making.

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Journal
Scientific Reports
Published
2026-07-25
DOI
https://doi.org/10.1038/s41598-026-61455-0
Primary Topic
Renal Diseases and Glomerulopathies
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article
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article

Histopathological predictors of renal outcomes in idiopathic membranous nephropathy with a focus on global sclerotic glomeruli ratio

Sim Kutlay, Necmi Eren, Mahmut Gök, Hayriye Sayarlıoğlu et al.
Scientific Reports
Renal Diseases and Glomerulopathies
article

Histopathological predictors of renal outcomes in idiopathic membranous nephropathy with a focus on global sclerotic glomeruli ratio

Sim Kutlay, Necmi Eren, Mahmut Gök, Hayriye Sayarlıoğlu, Melike Betül Öğütmen, Özkan Güngör, Alper Azak, Kültiğin Türkmen, Aydın Türkmen, Rümeyza Kazancioğlu, Yağmur Tahıllıoğlu, Nedim Yılmaz Selçuk, Taner Baştürk, Murat Duranay, Cuma Bülent Gul, Kenan Turgutalp, Onur Tunca, Cebrail Karaca, ERHAN TATAR, Mahmud İslam, Mevlüt Tamer Dinçer, HAMAD DHEİR, Sena Ulu, Şebnem Karakan, Arzu Özdemir, Garip Şahin, Hakki Arikan, Zülfükar Yilmaz, Tuba Elif Özler, Simal Koksal Cevher, Deren Oygar, Serap Yadigar, Mehmet Tanrisev, Sinan Kazan, Erkan Sengul, Belda Dursun, Abdulmecit Yildiz, Ferdi Karagoz, İsmail Kocyigit, Bulent Kaya, Ebru Gok Oguz
article en

Abstract

Abstract Idiopathic membranous nephropathy (MN) shows variable renal outcomes, and reliable histologic markers for risk stratification are limited. The global sclerotic glomeruli ratio (GSGR) may reflect chronic kidney damage and help predict progression, but its prognostic value and optimal threshold remain unclear. We retrospectively analyzed 322 patients with biopsy-proven idiopathic MN from the Turkish Society of Nephrology-Glomerular Diseases Study Group registry, excluding those with an estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m² at diagnosis or insufficient data. GSGR was calculated as the percentage of globally sclerotic glomeruli among total glomeruli. Histopathological parameters, including exudative glomerular changes, tubular atrophy/interstitial fibrosis (TA/IF), and vascular alterations, were semi-quantitatively graded according to the Renal Pathology Atlas (Fogo, 2022). Specifically, TA/IF was graded as: Grade 0 (< 5%), Grade 1 (5–25%), Grade 2 26–50%, and Grade 3 (> 50%) of cortical area involvement. Exudative changes were defined as intracapillary leukocyte accumulation and hyaline deposits in ≥ 25% of non-sclerotic glomeruli. The primary composite outcome was ≥ 50% eGFR decline from baseline, progression to eGFR < 15 mL/min/1.73 m², dialysis initiation, or kidney transplantation. Median follow-up was 60 months (IQR 48–72). Thirty patients (9.3%) reached the composite outcome. Receiver operating characteristic analysis identified a GSGR threshold of 15.7% (AUC 0.956; sensitivity 93.3%; specificity 82.7%). Patients with GSGR ≥ 15.7% had significantly higher event rates (35.1% vs. 1.2%; p < 0.001). In multivariate analysis, high GSGR, exudative changes, and response to immunosuppressive therapy independently predicted adverse outcomes. These associations remained significant across treatment subgroups. Sensitivity analyses confirmed these associations across multiple model specifications. Anti-PLA2R positivity correlated with higher baseline proteinuria but not independently with renal outcomes. A GSGR ≥ 15.7% is a strong, independent predictor of renal progression in idiopathic MN. Incorporating GSGR and exudative changes into risk stratification may improve prognostic assessment and therapeutic decision-making.

Scientific Reports
Sakarya University (TR), Balıkesir University (TR), Van Yüzüncü Yıl Üniversitesi (TR), Dicle University (TR), Trakya University (TR), Ministry of Health (TR), Bursa Uludağ Üni̇versi̇tesi̇ (TR), Izmir University (TR), Ankara University (TR), Bilkent University (TR), University of Health Science (KH), Ondokuz Mayıs University (TR), State Hospital (GB), Bezmiâlem Vakıf Üniversitesi (TR), Memorial Ankara Hospital (TR), Dr Lütfi Kırdar Kartal Eğitim ve Araştırma Hastanesi (TR), Necmettin Erbakan University (TR), Haseki Eğitim ve Araştırma Hastanesi (TR), Istanbul University-Cerrahpaşa (TR), Bakırköy Dr.Sadi Konuk Eğitim ve Araştırma Hastanesi (TR), Haydarpaşa Numune Eğitim ve Araştırma Hastanesi (TR), Başkent University Hospital (TR), Ergani Devlet Hastanesi (TR), Sağlık Bilimleri Üniversitesi (TR), Universidad CES (CO), Ankara Yıldırım Beyazıt University (TR), Şişli Etfal Eğitim ve Araştırma Hastanesi (TR), Afyonkarahisar Sağlık Bilimleri Üniversitesi, Kahramanmaraş Sütçü İmam University (TR), Pamukkale University (TR), Eskişehir Osmangazi University (TR), Mersin Üniversitesi (TR), Kocaeli Üniversitesi (TR), Afyon Kocatepe University (TR), Cukurova University (TR), Istanbul University (TR), Marmara University (TR), University of Health Sciences Antigua (AG), Erciyes University (TR)
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