Background. Although neutrophils and T cells are important in mediating renal injury following ischaemia/reperfusion, the role of macrophages is still unknown. Using liposomal clodronate (LC), we investigated the effect of systemic monocyte–macrophage depletion on renal damage in ischaemic acute renal failure in rats. Methods. Male Sprague–Dawley rats were injected by LC or liposomal vehicle and underwent bilateral renal pedicle clamping (40 min) or sham ischaemia. Biochemical and histological renal damage was assessed and gene expression kinetics of tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6 and monocyte chemoattractant protein-1 (MCP-1) using quantitative real-time reverse transcription–polymerase chain reaction were conducted at 4, 24 and 72 h after reperfusion. Results. The percentage of peripheral blood monocytes and ectodysplasin-1-positive cells in liver decreased significantly in LC-treated animals at 24 h. Systemic monocyte–macrophage depletion resulted in (a) less severe tubular necrosis, (b) reduced inflammation and (c) reduced apoptosis of renal tubular epithelial cells. Gene expression kinetics showed that IL-6 gene expression peaked early at 4 h after reperfusion, followed by TNF-α, IL-1β and MCP-1 expressions, which peaked at 24 h. Systemic monocyte–macrophage depletion significantly reduced these cytokine and chemokine gene expressions. Conclusions. These results suggest that macrophages are an important mediator in the initiation period of ischaemia/reperfusion injury and strategies that limit initial macrophage infiltration or activation can be useful in the treatment of acute renal failure.

Ryu SR, et al. J Korean Med Sci. 2017 Feb;32(2):249-256. https://doi.org/10.3346/jkms.2017.32.2.249

Background/Aim: Macrophages have been thought to play a role in renal tubulointerstitial fibrosis; recent reports have demonstrated an antifibrotic effect of macrophages in late-stage renal fibrosis. Liposome-encapsulated clodronate (LC) produces a selective and systemic depletion of phagocytic macrophages in vivo. To study the role of initial infiltrating macrophages in renal fibrosis, we compared the effects of pretreatment with LC and a liposome vehicle for control of the severity of renal fibrosis in a unilateral ureteral obstruction (UUO) rat model. Methods: One day after a single intravenous injection of LC or liposome vehicle, the rats underwent UUO. Following 1, 5, and 14 days, the kidneys were examined to evaluate macrophage infiltration and renal fibrosis. Results: LC depleted macrophages systemically and reduced renal fibrosis associated with UUO; this beneficial effect was accompanied by a decrease of transforming growth factor beta mRNA expression. The osteopontin expression was also reduced by pretreatment with LC. Conclusion: Initial interstitial infiltration of macrophages contributes to tubulointerstitial fibrosis in UUO.

The clinical importance of serum hepcidin in non-dialysis chronic kidney disease (CKD) patients is unclear. The database of a large-scale multicentre prospective study in Korea of 2238 patients enrolled from 2011–2016 was analysed. After excluding patients with missing serum hepcidin (n = 125) and haemoglobin (n = 23) levels, the study included 2090 non-dialysis CKD patients. Markers of inflammation and iron status were positively associated with serum hepcidin level, regardless of CKD stage. However, estimated glomerular filtration rate was inversely associated with serum hepcidin level, particularly in patients with CKD stages 3b–5 but not in those with CKD stages 1–3a. Use of erythropoiesis-stimulating agents was associated with increased serum hepcidin levels, particularly in patients with CKD stages 3b–5 but not in those with CKD stages 1–3a, and serum hepcidin levels positively correlated with the dose of erythropoiesis-stimulating agent. These findings suggest that serum hepcidin may be a uremic toxin and play an important role in erythropoietin resistance. However, future prospective studies are needed to confirm our results.