Institute for Molecular Medicine and Experimental Immunology, University Hospital of Bonn, Germany.
Department of Radiation Oncology, University Hospital of Bonn, Germany.
J Am Soc Nephrol. 2021 Oct;32(10):2445-2453. doi: 10.1681/ASN.2021010110. Epub 2021 Jun 18.
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.
肾去神经支配（RDN）是一种治疗药物抵抗性动脉高血压的侵袭性干预措施。其治疗价值存在争议。在这里，我们研究了 RDN 对小鼠炎症和感染性肾病模型的影响。
对小鼠进行单侧或双侧去神经支配或假手术，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性肾损伤（作为感染性肾损伤模型）。分析方法包括测量肾肾小球滤过率、蛋白尿、肾免疫细胞流式细胞术、免疫荧光显微镜检查以及通过光片荧光显微镜对光透明化肾组织进行三维成像，然后进行算法分析。
单侧 RDN 增加了去神经支配肾脏的肾小球滤过率，但降低了对侧肾脏的肾小球滤过率。在 NTN 模型中，更多的肾炎性抗体沉积在去神经支配肾脏的肾小球中，导致去神经支配的肾脏比未去神经支配的对侧肾脏表现出更强的炎症和损伤。此外，静脉注射 LPS 增加了去神经支配肾脏的中性粒细胞浸润和炎症，无论是单侧还是双侧 RDN 后。当我们在双侧去神经支配的小鼠中诱导肾盂肾炎时，双侧肾脏中的细菌和中性粒细胞都较少。在单侧去神经支配的小鼠中，肾盂肾炎减轻，去神经支配肾脏中的肾内中性粒细胞数量减少。未去神经支配的对侧肾脏中，即使与假手术组相比，也含有更多的细菌，并且表现出最强的中性粒细胞流入。
我们的数据表明，去神经支配肾脏中的灌注和过滤增加会深刻影响伴随的炎症性疾病。循环肾炎物质在肾脏中的沉积更高，因此在小鼠中，抗体和内毒素诱导的肾脏损伤加重。去神经支配的小鼠肾脏中的肾盂肾炎减轻，因为更高的肾小球滤过率有助于更好地用尿液冲洗细菌，代价是单侧去神经支配后对侧、未去神经支配的肾脏。
