Renal denervation (RDN) is an invasive intervention to treat drug-resistant arterial hypertension. Its therapeutic value is contentious. Here we examined the effects of RDN on inflammatory and infectious kidney disease models in mice.

Mice were unilaterally or bilaterally denervated, or sham operated, then three disease models were induced: nephrotoxic nephritis (NTN, a model for crescentic GN), pyelonephritis, and acute endotoxemic kidney injury (as a model for septic kidney injury). Analytical methods included measurement of renal glomerular filtration, proteinuria, flow cytometry of renal immune cells, immunofluorescence microscopy, and three-dimensional imaging of optically cleared kidney tissue by light-sheet fluorescence microscopy followed by algorithmic analysis.

Unilateral RDN increased glomerular filtration in denervated kidneys, but decreased it in the contralateral kidneys. In the NTN model, more nephritogenic antibodies were deposited in glomeruli of denervated kidneys, resulting in stronger inflammation and injury in denervated compared with contralateral nondenervated kidneys. Also, intravenously injected LPS increased neutrophil influx and inflammation in the denervated kidneys, both after unilateral and bilateral RDN. When we induced pyelonephritis in bilaterally denervated mice, both kidneys contained less bacteria and neutrophils. In unilaterally denervated mice, pyelonephritis was attenuated and intrarenal neutrophil numbers were lower in the denervated kidneys. The nondenervated contralateral kidneys harbored more bacteria, even compared with sham-operated mice, and showed the strongest influx of neutrophils.

Our data suggest that the increased perfusion and filtration in denervated kidneys can profoundly influence concomitant inflammatory diseases. Renal deposition of circulating nephritic material is higher, and hence antibody- and endotoxin-induced kidney injury was aggravated in mice. Pyelonephritis was attenuated in denervated murine kidneys, because the higher glomerular filtration facilitated better flushing of bacteria with the urine, at the expense of contralateral, nondenervated kidneys after unilateral denervation.

去肾神经术（RDN）是一种治疗耐药性动脉高血压的侵入性干预措施。其治疗价值存在争议。在这里，我们研究了 RDN 对小鼠炎症和传染性肾病模型的影响。

对小鼠进行单侧或双侧去神经，或假手术，然后诱导三种疾病模型：肾毒性肾炎（NTN，新月体肾炎模型）、肾盂肾炎和急性内毒素血症性肾损伤（作为脓毒性肾损伤模型）。分析方法包括测量肾小球滤过、蛋白尿、肾免疫细胞的流式细胞术、免疫荧光显微镜以及通过光片荧光显微镜对光学透明的肾组织进行三维成像，然后进行算法分析。

单侧 RDN 增加去神经肾脏的肾小球滤过，但减少对侧肾脏的肾小球滤过。在NTN模型中，更多的致肾炎抗体沉积在去神经支配的肾脏的肾小球中，导致去神经支配的肾脏比对侧非去神经支配的肾脏有更强的炎症和损伤。此外，在单侧和双侧 RDN 后，静脉注射 LPS 会增加去神经肾脏中的中性粒细胞流入和炎症。当我们在双侧去神经小鼠中诱导肾盂肾炎时，两个肾脏都含有较少的细菌和中性粒细胞。在单侧去神经的小鼠中，肾盂肾炎减弱，去神经的肾脏中肾内中性粒细胞数量较低。即使与假手术小鼠相比，未去神经支配的对侧肾脏也含有更多的细菌，并且显示出最强的中性粒细胞流入。

我们的数据表明，去神经支配的肾脏中灌注和滤过的增加可以深刻地影响伴随的炎症疾病。循环肾病物质的肾脏沉积较高，因此抗体和内毒素诱导的小鼠肾损伤加重。肾盂肾炎在去神经支配的小鼠肾脏中减弱，因为较高的肾小球滤过有助于更好地用尿液冲洗细菌，但在单侧去神经支配后，以牺牲对侧、非去神经支配的肾脏为代价。