Interstitial Fibrosis Severity Is Not Independently Associated with Anemia in Biopsy-Proven Primary Glomerulonephritis: A Nationwide Registry Analysis

Background and Objectives: Anemia is a frequent complication of chronic kidney disease (CKD), primarily attributed to erythropoietin deficiency. Interstitial fibrosis (IF), which disrupts the renal interstitium where erythropoietin-producing cells reside, may contribute to anemia independent of glomerular filtration rate (GFR). However, data in primary glomerulonephritis (PGN) are limited and conflicting. Materials and Methods: In this nationwide multicenter registry analysis (TSN-GOLD), 2794 adults with biopsy-proven PGN were included. Interstitial fibrosis was graded semi quantitatively (0–3). Anemia was defined according to KDIGO/WHO criteria. Multivariable logistic regression models were constructed to evaluate the independent association between IF severity and anemia, adjusting for age, sex, eGFR, log-transformed proteinuria, hypertension, diabetes mellitus, and biopsy diagnosis. Interaction between IF and eGFR was assessed. A predefined subgroup analysis was performed in patients with preserved renal function (eGFR ≥ 60 mL/min/1.73 m2). Results: Anemia was present in 34.4% of patients. Although moderate-to-severe IF was more frequent among anemic patients (p < 0.001), IF severity was not independently associated with anemia in multivariable analysis (p-trend = 0.72). Female sex and lower eGFR were independently associated with anemia. A statistically significant IF×eGFR interaction was observed (p = 0.0029), indicating effect modification across renal function levels. The model demonstrated moderate discrimination (AUC = 0.705). In patients with preserved renal function, IF severity was not associated with anemia. Conclusions: In this large multicenter cohort of PGN patients, interstitial fibrosis severity was not independently associated with anemia after adjustment for renal function and clinical covariates. These findings suggest that the association between interstitial fibrosis and anemia in PGN appears largely mediated by renal functional status rather than fibrosis severity alone.

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Journal
Medicina
Published
2026-04-25
DOI
https://doi.org/10.3390/medicina62050820
Primary Topic
Erythropoietin and Anemia Treatment
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article
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article

Interstitial Fibrosis Severity Is Not Independently Associated with Anemia in Biopsy-Proven Primary Glomerulonephritis: A Nationwide Registry Analysis

Meryem Timuçin, Alper Azak, Fatma Betül Güzel, Yasemin Özlük et al.
Medicina
Erythropoietin and Anemia Treatment
article

Interstitial Fibrosis Severity Is Not Independently Associated with Anemia in Biopsy-Proven Primary Glomerulonephritis: A Nationwide Registry Analysis

Meryem Timuçin, Alper Azak, Fatma Betül Güzel, Yasemin Özlük, Ömer Faruk Akçay, Sibel Gökçay Bek, Bülent Tokgöz, Kenan Turgutalp, Leyla Koç, Saime Paydaş, Meltem Gürsu, Müge Üzerk Kibar, Simge Bardak, Savaş Sipahi, İlhan Kurultak, Savaş Öztürk, Gültekin Süleymanlar, Mahmut Yavuz, Egemen Cebeci, Di̇lek Torun, Serdar Kahvecioğlu, Abdullah Şumnu, Siren Sezer, Serap Demir, Sena Ulu, Arzu Özdemir, Lütfullah Altıntepe, Mehmet Küçük, MEHMET KOÇ, Gülizar ŞAHİN, Zülfikar Yılmaz, Belda Dursun, Sim Kutlay, Garip Şahin, Dilek Taymez, Murat Duranay, Ali Rıza Odabaş, Ergün Parmaksız, Deren Oygar, İlter Bozacı, Nedim Yılmaz Selçuk, Caner Çavdar, Yaşar Yıldırım, Zeki Aydın, Tamer Sakacı, Serhan Pişkinpaşa, Nurhan Seyahi
article en

Abstract

Background and Objectives: Anemia is a frequent complication of chronic kidney disease (CKD), primarily attributed to erythropoietin deficiency. Interstitial fibrosis (IF), which disrupts the renal interstitium where erythropoietin-producing cells reside, may contribute to anemia independent of glomerular filtration rate (GFR). However, data in primary glomerulonephritis (PGN) are limited and conflicting. Materials and Methods: In this nationwide multicenter registry analysis (TSN-GOLD), 2794 adults with biopsy-proven PGN were included. Interstitial fibrosis was graded semi quantitatively (0–3). Anemia was defined according to KDIGO/WHO criteria. Multivariable logistic regression models were constructed to evaluate the independent association between IF severity and anemia, adjusting for age, sex, eGFR, log-transformed proteinuria, hypertension, diabetes mellitus, and biopsy diagnosis. Interaction between IF and eGFR was assessed. A predefined subgroup analysis was performed in patients with preserved renal function (eGFR ≥ 60 mL/min/1.73 m2). Results: Anemia was present in 34.4% of patients. Although moderate-to-severe IF was more frequent among anemic patients (p < 0.001), IF severity was not independently associated with anemia in multivariable analysis (p-trend = 0.72). Female sex and lower eGFR were independently associated with anemia. A statistically significant IF×eGFR interaction was observed (p = 0.0029), indicating effect modification across renal function levels. The model demonstrated moderate discrimination (AUC = 0.705). In patients with preserved renal function, IF severity was not associated with anemia. Conclusions: In this large multicenter cohort of PGN patients, interstitial fibrosis severity was not independently associated with anemia after adjustment for renal function and clinical covariates. These findings suggest that the association between interstitial fibrosis and anemia in PGN appears largely mediated by renal functional status rather than fibrosis severity alone.

MedicinaVol. 62(5)
Sakarya University (TR), Dicle University (TR), Trakya University (TR), Sivas Cumhuriyet Üniversitesi (TR), Ministry of Health (TR), Bursa Uludağ Üni̇versi̇tesi̇ (TR), Izmir University (TR), Selçuk University (TR), Ankara University (TR), University of Health Science (KH), Başkent University (TR), Dokuz Eylül University (TR), Akdeniz University (TR), State Hospital (GB), Bezmiâlem Vakıf Üniversitesi (TR), Istanbul Medipol University (TR), Batman University (TR), Dr Lütfi Kırdar Kartal Eğitim ve Araştırma Hastanesi (TR), Necmettin Erbakan University (TR), Sina Hospital (IR), Ankara Numune Eğitim ve Araştırma Hastanesi (TR), Haseki Eğitim ve Araştırma Hastanesi (TR), Istanbul University-Cerrahpaşa (TR), Bakırköy Dr.Sadi Konuk Eğitim ve Araştırma Hastanesi (TR), Education Training And Research (US), Sağlık Bilimleri Üniversitesi (TR), Izmir Bozyaka Eğitim ve Araştırma Hastanesi (TR), Gaziosmanpaşa Taksim Eğitim ve Araştırma Hastanesi (TR), Şişli Etfal Eğitim ve Araştırma Hastanesi (TR), S.B.Ü. Bursa Yüksek İhtisas Eğitim ve Araştırma Hastanesi (TR), 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 Medeniyet University (TR), Hacettepe University (TR), Istanbul University (TR), Marmara University (TR), University of Health Sciences Antigua (AG), Erciyes University (TR), Gazi University (TR)
Türk Nefroloji Dernegi
Gender equality
Openalex Percentile: Top 7%
Erythropoietin and Anemia Treatment
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