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Age-dependent plasma factor D levels and their clinical implications in complement-mediated kidney diseases
Abstract   Open access   Peer reviewed

Age-dependent plasma factor D levels and their clinical implications in complement-mediated kidney diseases

Angela Nelson, Yuzhou Zhang, Cecelia Fierce, Zachary Lynch, Carla Nester, Christopher Culek and Richard Smith
Immunobiology (1979), Vol.230(4), 153019
07/2025
DOI: 10.1016/j.imbio.2025.153019
url
https://doi.org/10.1016/j.imbio.2025.153019View
Published (Version of record) Open Access

Abstract

Complement Factor D (FD), also known as adipsin, is a serine protease essential for alternative pathway (AP) activation. Among complement proteins, it circulates at the lowest plasma concentration (1–2 mg/L in adults). As FD is primarily synthesized by adipocytes and catabolized through renal tubules, we sought to test two hypotheses. First, that FD levels in healthy children are significantly lower than those in adults reflecting differences in body mass index (BMI), and second, that FD levels in patients with chronic kidney disease are elevated independent of BMI. Plasma FD levels in EDTA samples were quantified using an ELISA (Hycult). A cohort of 159 healthy controls (age range: 1–65 years) without known complement disorders or inflammatory conditions was analyzed to establish normal reference levels, which were compared to FD levels in 145 subjects (age range: <1–82 years) with complement-mediated renal disease. FD levels were examined in relation to BMI and renal function. In healthy controls, FD levels strongly correlated with age (r = 0.83): in persons ≥20 years of age, the mean FD concentration was 1.07 mg/L (median: 1.12 mg/L, ±1 SD: 0.78–1.36 mg/L), while in persons <20 years of age, the mean FD level was significantly lower at 0.58 mg/L (median: 0.62 mg/L, ±1 SD: 0.41–0.75 mg/L). Among patients with complement -mediated kidney disease, FD levels correlated with chronic kidney disease (CKD) as measured by serum creatinine (r = 0.82) but did not correlate with age (r = 0.25). In the cohort with CKD, there was no correlation between FD levels and BMI (r = 0.29). This study defines age-specific FD reference ranges to improve the assessment of complement activity and kidney function in pediatric patients. In addition, we show that as kidney function deteriorates, FD levels increase independent of BMI. Given its role in AP activation, this increase in FD may contribute to complement dysregulation further exacerbating local kidney injury. Supported in part by National Institutes of HealthR01 DK110023.

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