P12 Proteostasis as a Therapeutic Target in Glomerular Injury

Abstract

Introduction: The molecular events occurring within the human kidney during treatment of lupus nephritis (LN) are unknown. We previously reported that the immune profile of LN biopsies at flare is different between complete responders (CR) from non-responders (NR). Here, we evaluate whether the differences in renal transcript expression after induction therapy can distinguish biopsies that end in CR and NR and identify a set of markers associated with treatment response and non-response. Methods: The expression of 511 immune-response genes was determined in kidney biopsies from 19 patients with proliferative LN and 4 normal controls using Nanostring technology. Biopsies were done at flare (Bx1) and after induction therapy (Bx2). After induction, 5 patients achieved CR, 4 patients had an NR and 10 patients achieved a PR by clinical metrics (24 hour urine proteinuria and serum creatinine). Results: Transcript expression was measured at Bx1 and Bx2 in all patients and compared to normal controls. Additionally, the change in expression from Bx1 and Bx2 was compared within each group and between groups. Transcripts were considered differentially expressed if they achieved both a p-value of <0.05 and at least a 1.5 fold change. From Bx1 to Bx2, transcripts that significantly changed in flares that ended in CR included increased expression of NCAM1 (FC-2.24, P¼0.004), and decreased expression of IL1RL1

FKN Facilitates HK-2 Cell EMT and Tubulointerstitial Lesions via the Wnt/β-Catenin Pathway in a Murine Model of Lupus Nephritis

“…Notably, if not controlled, LN can lead to renal failure and represents a significant cause of death in patients with SLE. Previously, the majority of studies that focused on LN stressed the importance of glomerular injury (5, 6). Recently, however, growing evidence demonstrates that the response of renal tubule lesions plays a vital role in the progression of renal disease (7).…”