PDGFR-β and kidney fibrosis

Abstract

Chronic kidney disease (CKD) is one of the fastest growing global causes of death, estimated to rank among the top five by 2040 (Foreman et al, 2018). This illustrates current pitfalls in diagnosis and management of CKD. Advanced CKD requires renal function replacement by dialysis or transplantation. However, earlier CKD stages, even when renal function is still normal, are already associated with an increased risk of premature death (Perez-Gomez et al, 2019). Thus, novel approaches to diagnose and treat CKD are needed. The histopathological hallmark of CKD is kidney fibrosis, which is closely associated with local inflammation and loss of kidney parenchymal cells. Thus, kidney fibrosis is an attractive process to develop tests allowing an earlier diagnosis of CKD and represents a potential therapeutic target to slow CKD progression or promote regression.

Figure 1. Clinical CKD progression versus kidney fibrosis and subsequent CKD progression induced by mesenchymal cell PDGFR‐β hyperactivity

(A) A simplified view of clinical CKD progression is provided. Diverse insults may lead to primary injury of diverse kidney cell types, setting in motion clinical manifestation and processes (e.g., hypertension, hematuria, proteinuria) that amplify injury, usually by recruiting inflammatory mediators, leading to loss of parenchymal renal cells and kidney fibrosis. Uremic, EPO‐deficient anemia is a feature of advanced CKD. (B) Experimental kidney fibrosis induced by mesenchymal cell PDGFR‐β hyperactivity. Kidney fibrosis is the earliest manifestation of kidney injury, predisposes to CKD progression in response to other insults, and is associated with early anemia. Of note, fibrosis clearly precedes other features of CKD such as inflammation and parenchymal cell injury and is not associated with hypertension, hematuria, or proteinuria. The potential uses of this new tool are indicated.