MO249: Characteristics of Glomerulonephritis (GN) with Dominant C1Q Precipitation Compared to Corresponding GN without C1Q Staining on Immunofluorescent Examination

Abstract BACKGROUND AND AIMS Although C1q nephropathy (C1QN) was introduced three decades ago, the clinical significance and renal outcomes of C1QN remain unclear. Furthermore, it is uncertain whether the diagnosis of C1QN could be a new pathologic entity with clinical meanings. This study aimed to compare the clinical characteristics of the GN reclassified into C1QN based on the criteria described by Jennette and Falk (Pediatr Nephrol 2010: 25: 1385–1396) and corresponding GN not included in C1QN. METHOD We enrolled 21 212 patients with native kidney biopsy between 1979 and 2018 from 18 hospitals throughout Korea, retrospectively. We primarily adopted the findings and diagnosis by the pathologist in each hospital and then reclassified into C1q nephropathy (C1QN) on the basis of the criteria as follows: (i) presence of ≥ 2 + C1q in the mesangium on immunofluorescence (IF), (ii) corresponding mesangial or para-mesangial electron dense deposits on electron microscopy (EM), and (iii) lack of clinical and pathological evidence of systemic lupus erythematosus. Among 21212 patients, 77 patients were selected as C1QN with the criteria; however, six patients were excluded because of presence of primary diseases, such as renal amyloidosis, Henoch-Schölein Nephritis and systemic vasculitis, and myeloma cast nephropathy. The data of final outcomes, incidences of end-stage renal disease (ESRD) and death, were gathered from each hospital’s data registry, from the ESRD registry of the Korean Society of Nephrology, and from the Statistics of Korea, and were merged based on the identifier of Koreans. The follow-up duration for ESRD was 69.1 ± 67.8 months and, for mortality, 77.9 ± 65.5 months. RESULTS There were pathologic findings of 71 patients reclassified into C1QN including 41 (57.7%) males. Mean age of patients were 42.9 ± 18.9 years. There were 9 (12.7%) patients with DM and 39 (54.9%) hypertensive patients. The levels of creatinine, eGFR, and UPCR were 1.24 ± 0.92 mg/dL, 84 ± 43 mL/min/1.73 m2 and 2.58 ± 2.80 g/g creatinine, respectively. There were 22 (31.0%) patients with eGFR < 60 mL/min/1.73 m2 and 22 (31.0%) patients with UPCR ≥ 3.5 g/g creatinine. There were various pathologic diagnoses classified into C1QN, such as, original C1QN (21), IgA nephropathy (IGAN) (21), membranous nephropathies (MN) (11), focal segmental glomerulosclerosis (7), mesangial glomerulopathy (6), diabetic nephropathy (3), minimal change lesion (1), and acute tubulointerstitial nephritis (1). We compared the characteristics among the pathologic finding classified into C1QN, the pathologic finding without C1q stain, and the pathologic finding with non-dominant C1q stain which did not fulfill the criteria of C1QN. The identified GNs, which included enough number of patients to compare, were FSGS, IGAN and MN. Some differences of clinico-pathologic findings and incidence of ESRD were not evident after re-analysis with groups matched age and gender with 1:3 manner between the GN re-categorized into C1QN and the corresponding GN without C1q staining. The only difference was lesser amount of proteinuria in MN patients re-classified into C1QN compared with MN patients without C1q staining. Immunoglobulins showed higher intensity in IF staining of C1QN compared with non-C1QN of the corresponding GN. Intensity of C3 was also higher in IGAN and MN re-categorized into C1QN compared with the corresponding IGAN and MN not included in C1QN, respectively. CONCLUSION Reclassification into C1QN with the pre-defined criteria did not indicate a different clinico-pathologic identity based on comparison with the original diagnosis of GN. Activation of C1q, presumed activation of classical complement pathway in kidney tissues, in so-called C1QN could not be classified into new disease entity. Further studies on this topic are needed.