TY - JOUR

T1 - Hemodialysis leads to plasma depletion of lectin complement pathway initiator molecule ficolin-2

AU - Nielsen, Ture Lange

AU - Pilely, Katrine

AU - Lund, Kit P.

AU - Warming, Peder Emil

AU - Plesner, Louis Lind

AU - Iversen, Kasper Karmark

AU - Garred, Peter

N1 - Funding Information: The authors want to thank Mr. Jesper Andresen and Ms. Jytte Bryde Clausen for technical assistance. Funding was obtained from the Danish Research Council for Independent Research (DFF‐6110‐00489), The Danish Heart Association (15‐R99‐A5943‐22922), The Svend Andersen Research Foundation, Rigshospitalet, and the Novo Nordisk Research Foundation. Funding Information: Danish Research Council for Independent Research, Grant/Award Number: DFF‐6110‐00489; Novo Nordisk Research Foundation; Rigshospitalet; The Danish Heart Association, Grant/Award Number: 15‐R99‐A5943‐22922; The Svend Andersen Research Foundation Funding information Publisher Copyright: © 2021 International Society for Hemodialysis

PY - 2021

Y1 - 2021

N2 - Introduction: This study aimed to investigate changes in complement system-related molecules in patients undergoing hemodialysis. Methods: Patients >18 years of age on maintenance hemodialysis were included. Using enzyme-linked immunosorbent assays (ELISA) methods complement related molecules ficolin-1, ficolin-2, ficolin-3 mannose-binding lectin, long pentraxin 3, complement activation products C3c, and complement activation potentials were measured before and after a single hemodialysis treatment. All patients were dialyzed with synthetic high flux filters >1.6 m2, respectively, Polyamix and Polysulfone, and the Kt/V was maintained >1.3. Findings: Three hundred and four patients were included. There was a modest decrease in plasma level of ficolin-1 (p < 0.001). Ficolin-2 was virtually depleted with median 3.9 (interquartile range [IQR]: 2.6–6.1, range 0.3–13.5) μg/ml before dialysis to median 0.0 (IQR: 0.0–0.5, range 0.0–5.5) μg/ml after dialysis (p < 0.001). No significant difference before and after hemodialysis was seen for mannose-binding lectin and long pentraxin 3 (p > 0.05). In a random subgroup of 160 patients ficolin-2-binding, ficolin-3-mediated lectin pathway capacity and classical pathway capacity were significantly decreased due to hemodialysis. The complement capacity of the alternative pathway was increased after hemodialysis (p = 0.0101), while mannose-binding lectin-mediated lectin pathway capacity was unaltered (p = 0.79). There was an increase in the complement activation product C3c (p < 0.0001), while the concentration of total C4 and C3 did not change (p > 0.158). Multivariate Cox proportional hazard analyses showed an increased risk for all-cause mortality with increasing ficolin-2 (p = 0.002) after hemodialysis. Discussion: Plasma ficolin-2 was virtually depleted from the circulation after hemodialysis. However, elevated plasma ficolin-2 levels after hemodialysis was independently associated with increased mortality.

AB - Introduction: This study aimed to investigate changes in complement system-related molecules in patients undergoing hemodialysis. Methods: Patients >18 years of age on maintenance hemodialysis were included. Using enzyme-linked immunosorbent assays (ELISA) methods complement related molecules ficolin-1, ficolin-2, ficolin-3 mannose-binding lectin, long pentraxin 3, complement activation products C3c, and complement activation potentials were measured before and after a single hemodialysis treatment. All patients were dialyzed with synthetic high flux filters >1.6 m2, respectively, Polyamix and Polysulfone, and the Kt/V was maintained >1.3. Findings: Three hundred and four patients were included. There was a modest decrease in plasma level of ficolin-1 (p < 0.001). Ficolin-2 was virtually depleted with median 3.9 (interquartile range [IQR]: 2.6–6.1, range 0.3–13.5) μg/ml before dialysis to median 0.0 (IQR: 0.0–0.5, range 0.0–5.5) μg/ml after dialysis (p < 0.001). No significant difference before and after hemodialysis was seen for mannose-binding lectin and long pentraxin 3 (p > 0.05). In a random subgroup of 160 patients ficolin-2-binding, ficolin-3-mediated lectin pathway capacity and classical pathway capacity were significantly decreased due to hemodialysis. The complement capacity of the alternative pathway was increased after hemodialysis (p = 0.0101), while mannose-binding lectin-mediated lectin pathway capacity was unaltered (p = 0.79). There was an increase in the complement activation product C3c (p < 0.0001), while the concentration of total C4 and C3 did not change (p > 0.158). Multivariate Cox proportional hazard analyses showed an increased risk for all-cause mortality with increasing ficolin-2 (p = 0.002) after hemodialysis. Discussion: Plasma ficolin-2 was virtually depleted from the circulation after hemodialysis. However, elevated plasma ficolin-2 levels after hemodialysis was independently associated with increased mortality.

KW - activation

KW - chronic kidney disease

KW - complement

KW - dialysis

KW - ficolin-2

U2 - 10.1111/hdi.12948

DO - 10.1111/hdi.12948

M3 - Journal article

C2 - 34132045

AN - SCOPUS:85108015188

VL - 25

SP - 479

EP - 488

JO - Hemodialysis International

JF - Hemodialysis International

SN - 1492-7535

IS - 4

ER -