363 Two boys with C3/DDD glomerulonephritis

Abstract

<h3></h3> A boy, 16 years of age. During routine analysis hematuria and proteinuria (up to 1.84 g/L) were found along with hypertension (max 160/70 mmHg). Physical examination showed no abnormailities. Total complement activity (classical pathway) of 7 CH50/ml (ref. 48-103 CH50/ml) and total complement activity (alternative pathway) of 0% (ref. 70-105%). C3 levels were low (median 0.06 g/L) while C4 were within reference ranges. Anti-C1q IgG autoantibody was 677 U/ml (ref. &lt;52), C3-nephritic factor 11,0% (ref. &lt;10%) and sC5b-9 (terminal complement complex) 1640 ng/mL (ref. 110-252 ng/mL). Complement factor I antigen was decreased 51% (ref. 70-130%) as well as complement factor B antigen of 45% (ref. 70-130%). These results support the presence of AP dysregulation with overactivation. <h3>Lupus aDNA negative</h3> Kidney biopsy revealed C3 glomerulonephritis. Due to nephritic syndrome the boy was treated with pulse methylprednisolone therapy, rituximab and cyclophosphamide. Until present, proteinuria was reduced (up to 0.48 g/L) with microhematuria. Due to a persistently low C3 and elevated sC5b-9, we are now considering Eculisumab as off label treatment option. Genetic analysis ongoing. Second boy, 5 years of age, was treated for nephritic syndrome in regional hospital. Physical examination showed no abnormailities. As significant proteinuria (3.62g/L) with low C3 was found. A kidney biopsy revealed Dense deposit disease. Total complement activity (classical pathway) 18 CH50/ml (ref. 48-103 CH50/ml) and total complement activity (alternative pathway) 0% (ref. 70-105%). C3 and C4 levels were low (0.1 and 0.06 g/L respectively). C3-nephritic factor was elevated 41,3% (ref. &lt;10%) as well as sC5b-9 (terminal complement complex) of 342 ng/mL (ref. 110-252 ng/mL). LDH was elevated of 552 U/L. Creatinine level was elevated at its highest of 198 µmol/L. Activity of the alternative and classical pathways were both deficient. Complement C3 and C4 levels are decreased, while those of factor I and B are in the normal range. The terminal pathway activity marker level is increased. The above results support a complement activation and consumption involving at least the classical pathway. The boy was treated with pulse methylprednisolone therapy, rituximab and cyclophosphamide. After initial therapy elevated serum creatinine levels decreased, as well as proteinuria. C3 stabilized around 0.50, C4 normalizes at 0.40, while proteinuria decreased to 0.9 g/L.