Macrophage as a therapeutic target for chronic kidney diseases

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Macrophage accumulation typically observed during progression of all kidney diseases and is potentially involved in the development of clinico-histopathological abnormalities observed as the disease progresses. These findings suggest that macrophages could be an important therapeutic target for chronic kidney diseases although their roles at the site of kidney lesion remain to be elucidated. We studied the mechanism of activated macrophage-mediated kidney injury using renal biopsy tissue, experimental model and culture system. Our studies on activated macrophages revealed that different macrophage phenotypes (M1 and M2) are involved in chronic glomerulonephritis with specific roles in different phases and lesions. The M1-activated macrophage, a pro-inflammatory phenotype, appeared to play a role in acute glomerular injury and was detected in active glomerular lesions such as cellular glomerular crescents and glomerular cell proliferations, and was suppressed by glucocorticoids. In contrast, the M2-activated phenotype, an anti-inflammatory phenotype, was more predominant in sites with chronic lesions such as glomerular sclerotic lesions and interstitial fibrosis, and was rather activated by glucocorticoids. Thus, macrophage phenotype-specific targeting, timing of treatment, and choice of therapeutic agents are vital in the prevention of macrophage-mediated renal injury.