Kidney Week

Abstract: TH-PO0447

C4d May Indicate Worse Prognosis in Primary FSGS

Session Information

• Glomerular Diseases: Autoimmune Diseases
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

• Zagorec, Nikola, Klinicka bolnica Dubrava Zavod za nefrologiju i dijalizu, Zagreb, Croatia

Nikola Zagorec, MD, PhD

• Kasumovic, Dino, Klinicka bolnica Dubrava Zavod za nefrologiju i dijalizu, Zagreb, Croatia

Dino Kasumovic, MD

• Kacinari, Patricia, Klinicka bolnica Dubrava Zavod za nefrologiju i dijalizu, Zagreb, Croatia

Patricia Kacinari, MD

• Abramovic, Ivana, Klinicka bolnica Dubrava Zavod za nefrologiju i dijalizu, Zagreb, Croatia

Ivana Abramovic, MD, DrMed

• Osmani, Besa, Klinicka bolnica Dubrava Zavod za nefrologiju i dijalizu, Zagreb, Croatia

Besa Osmani, DrMed

• Senjug, Petar, Klinicka bolnica Dubrava, Zagreb, Croatia

Petar Senjug, MD, PhD

• Horvatic, Ivica, Klinicka bolnica Dubrava Zavod za nefrologiju i dijalizu, Zagreb, Croatia

Ivica Horvatic, MD, PhD

• Ljubanovic, Danica Galesic, Klinicka bolnica Dubrava, Zagreb, Croatia

Danica Galesic Ljubanovic, MD, PhD

Background

Role of the complement system in pathogenesis of primary focal segmental glomerulosclerosis (pFSGS) in not clear. Here we aimed to explore a prognostic significance of C4d, a stabile marker of complement activation, in pFSGS.

Methods

A cohort of adult patients with pFSGS (full-blown nephrotic syndrome and diffuse podocyte processes effacement, form 2003-2021) was analyzed for presence of C4d (by immunochemistry). Samples with at leats one non-globally sclerotic glomeruli were analyzed and every glomerulus classified as segmentally sclerotic or nonsclerotic (NSG) and C4d positive or C4d negative. Based on the ratio of C4d positive non-GSG/total number of non-GSG and C4d positive NSG/total number of NSG, patients were stratified into two groups: >50% and <50%. Primary outcome was defined as composite of kidney failure (KF) or initial eGFR declining >50%. Treatment failure (TF) was defined as no at least partial remission of disease at last follow-up.

Results

A total of 58 patients were included (56.8% males, median age 50 (IQR 30-63.3)y). Median follow up was 90.7 (IQR 48-167) months. Table shows relevant demographic, histological and clinical data of our cohort as well as treatment and renal outcomes. Patients with >50% of C4d+ non-GSG had significantly higher 24-h proteinuria, higher proportion of TF (P=0.006) and worse renal survival (log-rank test, P=0.006). In multivariate Cox regression analysis, after inclusion of age, sex, initial eGFR and 24-h proteinuria, IFTA, serum albumin and C4d category, only C4d category (HR=4.077, 95% CI 1.101-15.09, P=0.035) and IFTA (HR=1.052, 95% CI 1.019-1.085, P=0.002) remained independently associated with progression to primary endpoint. Likewise, patients with >50% of C4d+ NSG of total number of NSG had higher proportion of TF (hi-square test, P=0.03) and worse renal survival (log-rank, P=0.037).

Conclusion

C4d seems to be independetly associated with disease progression, TF and worse renal survival in pFSGS. Presence of C4d in nonsclerotic glomeruli and its association with disease progression could indicate role of the complement system in pathogenesis of pFSGS independently of the presence of glomerular sclerosis.