Macrophage accumulation in human progressive diabetic nephropathy
Macrophage accumulation in human progressive diabetic nephropathy
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DOI：
10.1111/j.1440-1797.2006.00576.x
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发表时间：
2006-06-01
期刊：
影响因子：
2.5
通讯作者：
Chadban, Steven J.
中科院分区：
文献类型：
--
作者：
Nguyen, Duy;Ping, Fu;Chadban, Steven J.
背景：糖尿病肾病是一个重大的全球健康问题。进展为肾衰竭是常见的；然而，其机制尚不清楚。实验模型表明巨噬细胞的作用。因此，对巨噬细胞积聚及其与后续临床病程的关系进行了研究。方法：对连续20名组织学和临床诊断为糖尿病肾病的患者进行了至少5年的基线组织学和后续临床病程的回顾性研究。对肾活检组织中巨噬细胞积聚（KP-1/抗 CD68+ 细胞）、已知进展预测因素的基线测量（蛋白尿、肾小管间质损伤、肌成纤维细胞积聚）和 5 年进展（血清肌酐倒数图）之间的关系进行了量化。 结果：巨噬细胞积聚在肾小球中很明显 (2.8 + 糖尿病肾病患者的间质（296.9 + 63.3/mm(2) vs 19.0 + 1.3/mm(2)，P = 0.002）。肾小球巨噬细胞数量与基线血清肌酐相关（r = 0.548，P = 0.012），但与肾衰竭进展无关，因为肾小球巨噬细胞在早期糖尿病肾病中普遍存在，但在晚期糖尿病肾病中则不然。间质巨噬细胞积聚与血清肌酐（r = 0.649，P = 0.002）、蛋白尿（r = 0.779，P < 0.0001）、间质纤维化（r = 0.774，P < 0.0001）密切相关，并与 1/血清肌酐的斜率成反比（r = -0.531，P = 0.023).结论：巨噬细胞 糖尿病肾病的肾小球和间质内积聚，间质浸润的强度与随后肾功能下降的速度成正比。这些人类数据支持动物研究，表明巨噬细胞在糖尿病肾病中具有致病作用。
Background: Diabetic nephropathy is a major global health problem. Progression to renal failure is common; however, the mechanisms are unknown. Experimental models suggest a role for macrophages. Therefore, macrophage accumulation and its relationship to the subsequent clinical course were studied.Methods: A retrospective study of baseline histology and the subsequent clinical course over at least 5 years involving 20 consecutive patients with a histological and clinical diagnosis of diabetic nephropathy was performed. The relationship between macrophage accumulation in renal biopsy tissue (KP-1/anti-CD68+ cells), baseline measures of known predictors of progression (proteinuria, tubulointerstitial damage, myofibroblast accumulation) and progression over 5 years (plot of reciprocal of serum creatinine) was quantified.Results: Accumulation of macrophages was apparent in the glomeruli (2.8 + 0.7/gcs vs 1.0 + 0.2 for normals, P = not significant) and interstitium (296.9 + 63.3/mm(2)vs 19.0 + 1.3/mm(2) for normals, P = 0.002) of patients with diabetic nephropathy. Glomerular macrophage number correlated with baseline serum creatinine (r = 0.548, P = 0.012) but not with progression of renal failure as glomerular macrophages were prevalent in early, but not advanced diabetic nephropathy. Interstitial macrophage accumulation correlated strongly with serum creatinine (r = 0.649, P = 0.002), proteinuria (r = 0.779, P < 0.0001), interstitial fibrosis (r = 0.774, P < 0.0001) and inversely with the slope of 1/serum creatinine (r = -0.531, P = 0.023).Conclusion: Macrophages accumulate within glomeruli and the interstitium in diabetic nephropathy and the intensity of the interstitial infiltrate is proportional to the rate of subsequent decline in renal function. These human data support animal studies that suggest a pathogenic role for the macrophage in diabetic nephropathy.