Associations between nephron number and podometrics in human kidneys
Associations between nephron number and podometrics in human kidneys
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DOI：
10.1016/j.kint.2022.07.028
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发表时间：
2022-10-19
影响因子：
19.6
通讯作者：
Bertram, John F.
中科院分区：
文献类型：
--
作者：
Haruhara, Kotaro;Kanzaki, Go;Bertram, John F.
足细胞丢失和由此产生的肾单位丢失是肾小球硬化症和慢性肾病发展的常见过程。虽然肾小球硬化症的皮质分布是不均匀的，但非硬化性肾小球（NSG）数量、podometrics和podometrics中的区域差异之间的关系仍不完全清楚。为了帮助定义这一点，我们在横断面分析中研究了50例中位年龄为68岁、中位eGFR为73.5 mL/min/1.73m2且无明显肾小球疾病的成人尸检肾脏。使用物理解剖器/分离器组合估计每个肾脏的NSG数量，而使用基于模型的体视学估计podometrics。每个肾脏的NSG数量与每簇足细胞数量和足细胞密度直接相关。每个肾脏每增加100，000 NSG，每个肾小球足细胞增加26个，足细胞密度每增加106 mm 3足细胞增加16个。这些协会是独立的临床因素和皮质区。虽然每个肾小球的足细胞数量在三个区域中相似，但浅表肾小球最小，足细胞密度最高，但足细胞最小。增加年龄和高血压与较低的足细胞数量相关，年龄主要影响浅表肾小球，高血压主要影响髓质肾小球。因此，在这项首次报告NSG数量与足径之间直接相关的研究中，我们认为失去肾单位的NSG中足细胞数量正在减少。然而，另一种可能的解释可能是更多的肾单位可能会防止进一步的足细胞损失。
Podocyte loss and resultant nephron loss are common processes in the development of glomerulosclerosis and chronic kidney disease. While the cortical distribution of glomerulosclerosis is known to be non-uniform, the relationship between the numbers of non-sclerotic glomeruli (NSG), podometrics and zonal differences in podometrics remain incompletely understood. To help define this, we studied autopsy kidneys from 50 adults with median age 68 years and median eGFR 73.5 mL/min/1.73m2 without apparent glomerular disease in a cross-sectional analysis. The number of NSG per kidney was estimated using the physical dissector/fractionator combination, while podometrics were estimated using model-based stereology. The number of NSG per kidney was directly correlated with podocyte number per tuft and podocyte density. Each additional 100,000 NSG per kidney was associated with 26 more podocytes per glomerulus and 16 podocytes per 106 mm3 increase in podocyte density. These associations were independent of clinical factors and cortical zone. While podocyte number per glomerulus was similar in the three zones, superficial glomeruli were the smallest and had the highest podocyte density but smallest podocytes. Increasing age and hypertension were associated with lower podocyte number, with age mostly affecting superficial glomeruli, and hypertension mostly affecting juxtamedullary glomeruli. Thus, in this first study to report a direct correlation between the number of NSG and podometrics, we suggest that podocyte number is decreasing in NSG of individuals losing nephrons. However, another possible interpretation may be that more nephrons might protect against further podocyte loss.