Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
Department of Statistics, Leiden University Medical Center, Leiden, The Netherlands.
Nephrol Dial Transplant. 2017 Aug 1;32(8):1322-1329. doi: 10.1093/ndt/gfw260.
Inflammation plays a role in the development of diabetic nephropathy (DN) in type 2 diabetes. Although macrophages have been found in experimental models of DN, little is known regarding the presence of macrophages in patients with DN. Therefore, we investigated the presence and phenotype of glomerular and interstitial macrophages in relation to clinical and histopathological parameters in patients with DN.
Renal autopsy samples were obtained from 88 type 2 diabetic patients with histologically proven DN and stained for CD68 and CD163 as general and M2/anti-inflammatory markers of macrophages. Renal damage was scored based on histopathological classification of DN. Control renal autopsy samples were obtained from patients without renal abnormalities and from diabetic patients without DN. Positive cells per glomerulus were counted. Interstitial macrophages were counted semi-quantitatively.
Macrophages were present in all groups. In the DN group, the mean number of CD68+ cells per glomerulus and CD163+ cells per glomerulus was 4.2 (range 0-19) and 2.1 (range 0-14.47), respectively. The distribution was similar between all histopathological classes. Glomerular CD163+ macrophages were positively associated with DN class, interstitial fibrosis and tubular atrophy, and glomerulosclerosis. Interstitial CD68+ macrophages were correlated with glomerular filtration rate stage and albuminuria.
Our results demonstrate that macrophages are present in the glomeruli and interstitium of type 2 diabetic patients with DN and of controls. Although patients and controls had similar numbers of glomerular macrophages, glomerular anti-inflammatory CD163+ macrophages were associated with pathological lesions in DN. Taken together with the correlation between interstitial macrophages and interstitial fibrosis and tubular atrophy, DN class, and renal function, this finding suggests that macrophages may play a role in DN progression. Therefore, targeting macrophages may be a promising new therapy for inhibiting the progression of DN.
炎症在 2 型糖尿病患者的糖尿病肾病（DN）的发展中起作用。尽管在 DN 的实验模型中已发现巨噬细胞，但关于 DN 患者中巨噬细胞的存在却知之甚少。因此，我们研究了 DN 患者肾小球和间质巨噬细胞的存在及其与临床和组织病理学参数的关系。
从 88 例经组织学证实的 2 型糖尿病患者的肾尸检样本中获得了肾组织标本，并对 CD68 和 CD163 进行染色，以作为巨噬细胞的一般和 M2/抗炎标志物。根据 DN 的组织病理学分类对肾脏损伤进行评分。从无肾脏异常的患者和无 DN 的糖尿病患者中获得对照肾尸检样本。对每个肾小球的阳性细胞进行计数。间质巨噬细胞进行半定量计数。
巨噬细胞存在于所有组中。在 DN 组中，每个肾小球的 CD68+细胞和 CD163+细胞的平均数量分别为 4.2（范围 0-19）和 2.1（范围 0-14.47）。在所有组织病理学分类中，分布均相似。肾小球 CD163+巨噬细胞与 DN 分类，间质纤维化和肾小管萎缩以及肾小球硬化呈正相关。间质 CD68+巨噬细胞与肾小球滤过率阶段和蛋白尿相关。
我们的结果表明，巨噬细胞存在于 2 型糖尿病伴 DN 患者和对照者的肾小球和间质中。尽管患者和对照者的肾小球巨噬细胞数量相似，但肾小球抗炎性 CD163+巨噬细胞与 DN 的病理病变有关。结合间质巨噬细胞与间质纤维化和肾小管萎缩，DN 分类和肾功能之间的相关性，这一发现表明巨噬细胞可能在 DN 的进展中起作用。因此，靶向巨噬细胞可能是抑制 DN 进展的一种有前途的新疗法。
