ESPN 54th Annual Meeting

ESPN 2022


 
Plasma soluble terminal complement complex C5b-9 is associated with acute glomerular histological lesions in children with kidney disease
Eugénie Fradette 1 Natalie Patey 1 Arnaud Bonnefoy 2 Alexandra Cambier 3 Stéphan Troyanov 4 Anne-Laure Lapeyraque 3 Adrien Flahault 5

1- Department of Pathology, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada
2- Hematology division, Department of Pediatrics, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada
3- Nephrology division, Department of Pediatrics, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada
4- Nephrology division, Department of Medicine, Hôpital du Sacré-Coeur de Montréal, Montreal, Quebec, Canada
5- Nephrology division, Hôpital Européen Georges Pompidou, Paris, France
 
Introduction:

Complement activation plays a central role in the pathophysiology of glomerulonephritis. This study aimed to determine if urine and plasma levels of soluble terminal complement complex C5b-9 (sC5b-9) reflect complement activity defined by C5b-9 deposits associated with glomerular and tubular histological lesions.

Material and methods:

We conducted a retrospective study of 61 kidney biopsy samples in children between 2018 and 2021.Urine and plasma samples were collected just before the kidney biopsy, to assess standard biochemical assays, plasma and urine sC5b-9. Biopsy specimens were examined in a blinded fashion by two operators using indirect immunohistochemistry against C5b-9 in paraffin-embedded sections. We quantified glomerular and tubular deposition of C5b-9 and calculated scores for active and chronic lesions. Chronic lesions were defined by percentage of glomerular sclerosis, segmental hyalin glomerular lesions and atrophic tubules. Active lesions were characterized by all other, non-chronic, lesions.

Results:

Median (interquartile range) age of patients at biopsy was 14 (9, 16) years. Seventeen (28%) were follow-up kidney transplant biopsies. Median eGFR (defined the Schwartz formula) was 89 (77, 99) ml/min/1.73 m2. Median plasma sC5b-9 was 166 (124, 273) ng/ml, and median urine sC5b-9 to creatinine ratio was 1.28 (0.56, 2.69) ng/mmol. Plasma sC5b-9 was significantly associated with active (p=0.019), but not chronic glomerular lesions. Conversely, urinary sC5b-9 to creatinine ratio was significantly associated with chronic (p=0.024), but not active, glomerular lesions. No biomarker was associated with tubular activity. We found no significant association of plasma or urine sC5b-9 with clinical and biological characteristics.

Conclusions:

Plasma sC5b-9 is associated with histological acute glomerular activity whereas urinary sC5b-9 is associated with chronic glomerular lesions. Future studies are needed to determine whether plasma and urine sC5b-9 levels may be used as surrogates of renal biopsy to assess progression and treatment of kidney disease.