Lundberg S, Lundahl J, Gunnarsson I, Jacobson S H
Nephrology Unit, Division of Medicine, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden.
Clin Nephrol. 2010 Mar;73(3):221-8. doi: 10.5414/cnp73221.
IgA nephropathy (IgAN), the most common chronic inflammatory kidney disease, implies a considerable risk of renal failure and premature cardiovascular disease. Metabolic activation of monocytes has been suggested to be an important link between chronic inflammation, oxidative stress and the development of atherosclerosis. Oxidative stress is also involved in the progression of kidney disease. In this study we investigated the degree of monocyte activation, measured by monocyte respiratory burst in patients with IgAN, since these patients represent a fairly homogenous group of patients with chronic kidney disease, and compared the results to those in healthy subjects. As anti- inflammatory effects have been ascribed to HMG-reductase inhibitors, we also examined whether treatment with atorvastatin influenced monocyte respiratory burst.
Monocyte respiratory burst, unstimulated and stimulated by fMLP and PMA, was measured by flow cytometry in 16 patients with biopsy proven IgAN before and after 1 month of treatment with 20 mg atorvastatin/ day. Baseline values were compared to measurements in healthy subjects. Blood and urine samples, before and after statin treatment, were also analyzed for ox-LDL, inflammatory markers (CRP, MCP-1, ICAM-1, TNFR II and NGAL/MMP-9) and renal functional parameters.
At baseline, respiratory burst of PMA-stimulated monocytes was higher in patients with IgAN as compared to that in healthy subjects (p = 0.002). After atorvastatin treatment there was a significant reduction of unstimulated, fMLP- and PMA-stimulated monocyte respiratory burst compared to baseline values (p = 0.03, p = 0.003 and p = 0.002, respectively). For ox-LDL and inflammatory serum markers we observed no significant changes.
Our study demonstrates a higher monocyte respiratory burst in patients with IgAN compared to in cells from healthy controls as well as a significant reduction of this parameter after short time and low dose atorvastatin treatment.
IgA肾病（IgAN）是最常见的慢性炎症性肾脏疾病，意味着存在相当大的肾衰竭和心血管疾病过早发生的风险。单核细胞的代谢激活被认为是慢性炎症、氧化应激与动脉粥样硬化发展之间的重要联系。氧化应激也参与肾脏疾病的进展。在本研究中，我们调查了IgAN患者中通过单核细胞呼吸爆发测量的单核细胞激活程度，因为这些患者代表了一组相当同质的慢性肾病患者，并将结果与健康受试者进行比较。由于已将抗炎作用归因于HMG-还原酶抑制剂，我们还研究了阿托伐他汀治疗是否会影响单核细胞呼吸爆发。
通过流式细胞术在16例经活检证实为IgAN的患者中测量未刺激以及由fMLP和PMA刺激后的单核细胞呼吸爆发，这些患者接受每日20mg阿托伐他汀治疗1个月前后。将基线值与健康受试者的测量值进行比较。还对他汀类药物治疗前后的血液和尿液样本进行了氧化型低密度脂蛋白（ox-LDL）、炎症标志物（CRP、MCP-1、ICAM-1、TNFR II和NGAL/MMP-9）以及肾功能参数的分析。
在基线时，与健康受试者相比，IgAN患者中PMA刺激的单核细胞呼吸爆发更高（p = 0.002）。阿托伐他汀治疗后，与基线值相比，未刺激的、fMLP和PMA刺激的单核细胞呼吸爆发均显著降低（分别为p = 0.03、p = 0.003和p = 0.002）。对于ox-LDL和炎症血清标志物，我们未观察到显著变化。
我们的研究表明，与健康对照细胞相比，IgAN患者的单核细胞呼吸爆发更高，并且在短时间和低剂量阿托伐他汀治疗后该参数显著降低。
