The Role of Complement and JAK/STAT Pathway in IgA Nephropathy

Background: IgA nephropathy is the most frequent primary glomerulopathy worldwide and an important cause of End-Stage Renal Disease. The pathophysiology of the disease is not very well established and complement-activation pathways is involved in IgAN. JAK/STAT signaling pathway may play an important role in the pathogenesis of the disease. Methods: A retrospective analysis was performed on all IgAN patients diagnosed by kidney biopsy between 2002 and 2016. Clinical and laboratory data were collected at baseline and at the end of follow up. Kidney tissue sections were stained with antibodies specific for CD68 and for components of JAK-STAT pathway, including JAK2, JAK3, p-STAT and STAT3. As controls 6 renal tumor border tissues were used. CD68 positive cells were quantified in glomeruli and tubulointerstitium and correlated with MEST score. Results: Clinical features are summarized in Table 1. Mean follow-up time in the study population was 102 months. More than half of patients achieved remission and 31.1% achieved the primary outcome primary outcome that was defined as ESRD or doubling of baseline creatinine. Staining for JAK3 was observed observed in the renal tubule and glomeruli. Staining for JAK3 was enhanced in patients with IgAN compared to controls. Interstitial CD68-positive cells showed correlation with initial and final eGFR, proteinuria and intersticial fibrosis. Logistic regression analysis showed that CD68-positive cells were significantly associated with progression to ESRD and hematuria. Conclusion: The role of complement and JAK/STAT pathway in IgAN may provide potential targets and rationale for development of targeting therapy of the disease. Clinical and laboratory data at the time of biopsy and at the end of follow-up - n 63 Age (years) 33.00 [24.50-46.00] Woman (n,%) 35 (55.6) Not White (n,%) 17 (27.0) Creatinine mg/dL 1.39 [0.94-2.21] eGFR CKD-EPI (ml/min/1,73 m2) 58.00 [31.00-95.00] Proteinuria g/day 1.60 [1.11-3.06] Hematuria (n,%) 54 (85.7) Follow up (months) 102.00 [34.00-144.50] Delta eGFR/year -1.19 [-3.95-(-0.19)] Remission (n,%) 31 (54.4) Creatinine duplication or ESRD (n,%) 19 (31.1)