The specific roles of renal macrophages in monitoring and clearing off intratubular particles

ABSTRACT During the filtrate of the glomerulus flows though the renal tubular system, a variety of microscopic sediment particles, including mineral crystals resulting from urine concentration, are generated. Dislodging these particles in the intratubular compartment is critical to ensure free flow of filtrate and the final formation of urine. However, the underlying mechanism for the clearance is unclear. Here, using high-resolution microscopy, we uncovered that the juxtatubular macrophages in the medulla constitutively formed transepithelial protrusions and were “sampling” urine contents. These behaviors were strengthened in the development of nephrolithiasis. In particular, the juxtatubular macrophages were efficient in sequestering and phagocytosing intraluminal sediment particles, and occasionally making transmigration to the tubule lumen to escort the excretion of urine particles. Specific depletion of renal macrophages precipitated kidney stone formation and aggravated the accompanied inflammation upon hyperoxaluria challenge. Thus, renal macrophages undertake a specific role in maintaining the tubular system unobstructed.