Department of Nephrology, Molecular Cell Lab for Kidney Disease, Shanghai Peritoneal Dialysis Research Center, Renji Hospital, Uremia Diagnosis and Treatment Center, Shanghai Jiaotong University, School of Medicine, China.
Department of Nephrology, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, School of Medicine, China.
Diabetes Res Clin Pract. 2024 Mar;209:111594. doi: 10.1016/j.diabres.2024.111594. Epub 2024 Feb 24.
The relationship between Bowman's capsule thickening and progression of diabetic kidney disease (DKD) remains uncertain.
Renal biopsy specimens from 145 DKD patients and 20 control subjects were evaluated for Bowman's capsule thickness. Immunohistochemical staining assessed col4α2, laminin β1, and albumin expression. In a discovery cohort of 111 DKD patients with eGFR ≥ 30 ml/min/1.73 m, thickening was classified as fibrotic or exudative. The composite endpoint included CKD stage 5, dialysis initiation, and renal disease-related death. Prognosis was analyzed using Kaplan-Meier and Cox regression analyses. Two validation cohorts were included.
Three types of thickening were observed: fibrotic, exudative, and periglomerular fibrosis. Parietal epithelial cell matrix protein accumulation contributed to fibrotic thickening, while albumin was present in exudative thickening. Bowman's capsule was significantly thicker in DKD patients (5.74 ± 2.09 μm) compared to controls (3.38 ± 0.43 μm, P < 0.01). In discovery cohort, the group of exudative thickning had a poorer prognosis(median time 20 months vs 57 months, P = 0.000). Cox multivariate analysis revealed that exudative thickening of Bowman's capsule were associated with a poor prognosis. The validation cohorts confirmed the result.
Various mechanisms contribute to Bowman's capsule thickening in DKD. The proportion of exudative thickening may serve as a valuable prognostic indicator for DKD patients.
目前尚不清楚鲍曼囊增厚与糖尿病肾病(DKD)进展之间的关系。
对 145 例 DKD 患者和 20 例对照的肾活检标本进行鲍曼囊厚度评估。免疫组织化学染色评估 col4α2、层粘连蛋白β1 和白蛋白的表达。在 eGFR≥30ml/min/1.73m 的 111 例 DKD 患者的发现队列中,将增厚分为纤维性或渗出性。复合终点包括 CKD 第 5 期、开始透析和与肾脏疾病相关的死亡。使用 Kaplan-Meier 和 Cox 回归分析进行预后分析。纳入了两个验证队列。
观察到三种类型的增厚:纤维性、渗出性和肾小球旁纤维性。壁层上皮细胞基质蛋白堆积导致纤维性增厚,而白蛋白存在于渗出性增厚中。与对照组(3.38±0.43μm,P<0.01)相比,DKD 患者的鲍曼囊明显更厚(5.74±2.09μm)。在发现队列中,渗出性增厚组预后较差(中位时间 20 个月 vs 57 个月,P=0.000)。Cox 多变量分析显示,鲍曼囊的渗出性增厚与预后不良相关。验证队列证实了这一结果。
DKD 中鲍曼囊增厚的机制各异。渗出性增厚的比例可能是 DKD 患者的一个有价值的预后指标。