Depleting profibrotic macrophages using bioactivated in vivo assembly peptides ameliorates kidney fibrosis

Managing renal fibrosis is challenging owing to the complex cell signaling redundancy in diseased kidneys.Renal fibrosis involves an immune response dominated by macrophages,which activates myofibroblasts in fibrotic niches.However,macrophages exhibit high heterogeneity,hindering their potential as therapeutic cell targets.Herein,we aimed to eliminate specific macrophage subsets that drive the profibrotic immune response in the kidney both temporally and spatially.We identified the major profibrotic macrophage subset(Fn1+Spp1+Arg1+)in the kidney and then constructed a 12-mer glycopeptide that was designated as bioactivated in vivo assembly PK(BIVA-PK)to deplete these cells.BIVA-PK specifically binds to and is internalized by profibrotic macrophages.By inducing macrophage cell death,BIVA-PK reshaped the renal microenvironment and suppressed profibrotic immune responses.The robust efficacy of BIVA-PK in ameliorating renal fibrosis and preserving kidney function highlights the value of targeting macrophage subsets as a potential therapy for patients with CKD.

具有肾脏意义的单克隆免疫球蛋白病合并低尿酸血症1例

具有肾脏意义的单克隆免疫球蛋白病(monoclonal gammopathy of renal significance,MGRS)为良性或癌前血液系统疾病,常常发生进展性肾脏病和终末期肾病,最常见的临床表现为肾功能损害和蛋白尿,伴或不伴血尿[1]。MRGS肾脏损害病理表现多样,有文献报道MGRS导致的轻链近端小管病。