BACKGROUND AND AIMS: Complement system seems to play an important role in the pathogenesis of Acute Kidney Injury (AKI). The aim of this study was to investigate the role of complement system in the pathogenesis of human AKI. For this purpose, we studied Membrane Attack Complex (MAC) and factor H in plasma and kidney tissue in AKI. METHODS: Plasmatic concentrations of MAC and Factor H were studied in patients with hospital-acquired AKI and their respective controls. MAC and Factor H expression and localization within the kidney were studied by immunohistochemistry in kidney tissue samples from autopsies. Demographical, past medical, and laboratory data in patients on admission and 3 years after discharge were recorded. RESULTS: Plasmatic MAC concentrations were significantly higher in AKI-patients (5848±3604 vs 3703±1483 mAU/mL, p< 0.01), mainly in the severe cases, as measured by the need of renal replacement therapy, non-recovery of renal function, RIFLE classification and CKD development. MAC deposition was observed in tubular epithelial cell basal membranes, showing a larger number of tubules with MAC deposition, larger perimeter of affected tubules and greater intensity of MAC immunostaining in AKI patients. Factor H concentrations were higher in AKI patients (0.86±0.05 vs 0.60±0.04 mg/mL, p=0.007), showing a strong positive association with plasmatic MAC (r=0.7, p< 0.01)). Factor H immunostaining showed a tubular cytoplasmic pattern, with significant variations in the staining intensity, associated with the severity of histologic damage. CONCLUSION: Our data confirm that complement system is involved in human AKI, through the lytic action of MAC in tubular epithelial cells. These results suggest that complement system activation in AKI could be related with CKD development.
BACKGROUND AND AIMS: Complement system seems to play an important role in the pathogenesis of Acute Kidney Injury (AKI). The aim of this study was to investigate the role of complement system in the pathogenesis of human AKI. For this purpose, we studied Membrane Attack Complex (MAC) and factor H in plasma and kidney tissue in AKI. METHODS: Plasmatic concentrations of MAC and Factor H were studied in patients with hospital-acquired AKI and their respective controls. MAC and Factor H expression and localization within the kidney were studied by immunohistochemistry in kidney tissue samples from autopsies. Demographical, past medical, and laboratory data in patients on admission and 3 years after discharge were recorded. RESULTS: Plasmatic MAC concentrations were significantly higher in AKI-patients (5848±3604 vs 3703±1483 mAU/mL, p< 0.01), mainly in the severe cases, as measured by the need of renal replacement therapy, non-recovery of renal function, RIFLE classification and CKD development. MAC deposition was observed in tubular epithelial cell basal membranes, showing a larger number of tubules with MAC deposition, larger perimeter of affected tubules and greater intensity of MAC immunostaining in AKI patients. Factor H concentrations were higher in AKI patients (0.86±0.05 vs 0.60±0.04 mg/mL, p=0.007), showing a strong positive association with plasmatic MAC (r=0.7, p< 0.01)). Factor H immunostaining showed a tubular cytoplasmic pattern, with significant variations in the staining intensity, associated with the severity of histologic damage. CONCLUSION: Our data confirm that complement system is involved in human AKI, through the lytic action of MAC in tubular epithelial cells. These results suggest that complement system activation in AKI could be related with CKD development.
Authors: Erin K Stenson; Zhiying You; Ron Reeder; Jesse Norris; Halden F Scott; Bradley P Dixon; Joshua M Thurman; Ashley Frazer-Abel; Peter Mourani; Jessica Kendrick Journal: Kidney360 Date: 2021-10-07
Authors: Carlos E Arias-Cabrales; Marta Riera; María José Pérez-Sáez; Javier Gimeno; David Benito; Dolores Redondo; Carla Burballa; Marta Crespo; Julio Pascual; Eva Rodríguez Journal: Clin Kidney J Date: 2020-10-10
Authors: Jacob J E Koopman; Mieke F van Essen; Helmut G Rennke; Aiko P J de Vries; Cees van Kooten Journal: Front Immunol Date: 2021-02-11 Impact factor: 7.561
Authors: Carlos Arias-Cabrales; Eva Rodriguez-Garcia; Javier Gimeno; David Benito; María José Pérez-Sáez; Dolores Redondo-Pachón; Anna Buxeda; Carla Burballa; Marta Crespo; Marta Riera; Julio Pascual Journal: J Clin Med Date: 2021-03-02 Impact factor: 4.241