Bao Daorina, Zhang Xu, Wang Su-Xia, Wang Yu, Zhao Ming-Hui
Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.
Institute of Nephrology, Peking University, Beijing, China.
Kidney Res Clin Pract. 2025 Jul;44(4):626-637. doi: 10.23876/j.krcp.23.266. Epub 2024 Sep 11.
The current study was initiated to evaluate renal nucleotide-binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome pathway activation and macrophage subtype distribution and their clinicopathological significance in a cohort of oxalate-induced acute kidney injury.
Twelve patients with biopsy-proven acute oxalate nephropathy (AON) from January 2016 to October 2022 were retrospectively enrolled, with estimated glomerular filtration rate (eGFR)-matched 24 patients with acute tubulointerstitial nephritis (ATIN) as disease control. Pathological lesions as well as markers of NLRP3 inflammasome pathway and macrophage phenotype detected by immunohistochemistry staining were semi-quantitatively analyzed.
Oxalate depositions were found in 5% to 20% of tubules with a positive correlation with Sirius Red staining in AON specimens (rp = 0.668, p = 0.02). Disruption of tubular basement membrane and inflammatory cell reaction was more prominent in specimens of AON (both p < 0.05) as compared with ATIN specimens. The expressions of NLRP3, caspase-1, and gasdermin D were significantly increased in AON specimens as well (all p < 0.05). Patients with M1/M2 macrophage ratio <1 were found with more chronic tubulointerstitial lesions and presented with lower eGFR at the last follow-up (24.8 ± 10.6 mL/min/1.73 m2 vs. 55.1 ± 21.2 mL/ min/1.73 m2, p = 0.02) in the AON group.
The NLRP3 inflammasome pathway was activated in the kidneys of AON patients, and the ratio of M1 and M2 macrophages was associated with chronicity of pathological changes, which needs further exploration.
本研究旨在评估草酸盐诱导的急性肾损伤队列中肾核苷酸结合寡聚化结构域样受体家族含吡啉结构域3（NLRP3）炎性小体途径的激活、巨噬细胞亚型分布及其临床病理意义。
回顾性纳入2016年1月至2022年10月间12例经活检证实的急性草酸盐肾病（AON）患者，并选取估算肾小球滤过率（eGFR）匹配的24例急性肾小管间质性肾炎（ATIN）患者作为疾病对照。对病理病变以及通过免疫组织化学染色检测的NLRP3炎性小体途径标志物和巨噬细胞表型进行半定量分析。
在AON标本中，5%至20%的肾小管发现草酸盐沉积，且与天狼星红染色呈正相关（rp = 0.668，p = 0.02）。与ATIN标本相比，AON标本中肾小管基底膜破坏和炎症细胞反应更明显（均p < 0.05）。AON标本中NLRP3、半胱天冬酶 - 1和gasdermin D的表达也显著增加（均p < 0.05）。在AON组中，M1/M2巨噬细胞比率<1的患者发现有更多慢性肾小管间质病变，且在最后一次随访时eGFR较低（24.8±10.6 mL/min/1.73 m² 对比55.1±21.2 mL/min/1.73 m²，p = 0.02）。
AON患者肾脏中NLRP3炎性小体途径被激活，M1和M2巨噬细胞的比例与病理变化的慢性程度相关，这需要进一步探索。
