The relationship between albuminuria, MCP-1/CCL2, and interstitial macrophages in chronic kidney disease

Abstract

Glomerular-derived proteins may activate tubular cells to express the macrophage-directed chemokine monocyte chemoattractant protein-1 (MCP-1/CCL2). Macrophages at interstitial sites have a central role in directing renal scarring. We have prospectively assessed the relationship between albuminuria, urinary MCP-1/CCL2, interstitial macrophage infiltration, in situ damage, and clinical outcomes in a large group of patients with chronic kidney disease. We studied 215 patients and quantified albumin-creatinine ratio (ACR), urinary MCP-1/CCL2, interstitial macrophage numbers, and in situ damage. ACR correlated with urinary MCP-1/CCL2 (correlation 0.499; P<0.001), interstitial macrophage numbers (correlation 0.481; P<0.001), and index of chronic damage (correlation 0.363; P<0.001). Macrophage numbers closely correlated with in situ damage (correlation 0.755; P<0.001). By multivariate analysis ACR, urinary MCP-1/CCL2, and interstitial macrophage numbers were interdependent. By Kaplan-Meier survival analysis albuminuria, urinary MCP-1/CCL2, interstitial macrophages, and chronic damage predict the outcome. ACR, macrophage numbers, chronic damage, and creatinine independently predicted renal survival. The association of ACR with other variables was strongest in patients with less advanced disease states. There is a close association between albuminuria, urinary MCP-1/CCL2, and interstitial macrophage infiltration with in situ damage and clinical outcomes. These findings support the hypothesis that albuminuria triggers tubular MCP-1/CCL2 expression with subsequent macrophage infiltration. These processes may represent the dominant pathway for the progression of renal injury before the establishment of advanced renal scarring.

Nanomedicine engulfed by macrophages for targeted tumor therapy

“…This distinction of targeting ability was due to the higher chemotactic cytokine (such as CCL2) expression in the tumor tissues of immunocompetent mice than that of immunodeficiency mice (Figure 7E), since the overexpressing CCL2 chemokine is the dominant factor responsible for the homing ability of macrophages, inducing the macrophages for accumulation. 28,29 As expected, no obvious fluorescence signal was observed in the Kunming mice injected with the negative control of free Cypate.…”

How Does Proteinuria Cause Progressive Renal Damage?

“…A strong relationship was found between proteinuria and MCP-1-mediated interstitial damage in a prospective study of patients who underwent renal biopsy for chronic renal disease (61). High levels of albuminuria, urinary MCP-1, and interstitial macrophages were predictive of doubling in serum creatinine and/or endstage renal failure.…”

“…MCP-1 expression that is driven by excess plasma protein signaling consistently seems to represent an important pathway for progression of injury in humans (61). A strong relationship was found between proteinuria and MCP-1-mediated interstitial damage in a prospective study of patients who underwent renal biopsy for chronic renal disease (61).…”

Differential Ly6C Expression after Renal Ischemia-Reperfusion Identifies Unique Macrophage Populations

“…12,13 In fact, CKD patients with high levels of interstitial macrophage infiltration have the poorest renal outcome. 14 Macrophages are a heterogeneous cell population that can switch from one phenotype to another in response to extracellular cues. 15 In vitro studies have defined the classically activated macrophages as proinflammatory, M1 macrophages, whereas the alternatively activated, M2 macrophages typically modulate the immune response to promote repair and fibrosis.…”