Puelles Victor G, Douglas-Denton Rebecca N, Cullen-McEwen Luise A, Li Jinhua, Hughson Michael D, Hoy Wendy E, Kerr Peter G, Bertram John F
Department of Anatomy and Developmental Biology, Monash University, Melbourne, Australia;
Department of Pathology, University of Mississippi Medical Center, Jackson, Mississippi;
J Am Soc Nephrol. 2015 Sep;26(9):2277-88. doi: 10.1681/ASN.2014070641. Epub 2015 Jan 7.
Increases in glomerular size occur with normal body growth and in many pathologic conditions. In this study, we determined associations between glomerular size and numbers of glomerular resident cells, with a particular focus on podocytes. Kidneys from 16 male Caucasian-Americans without overt renal disease, including 4 children (≤3 years old) to define baseline values of early life and 12 adults (≥18 years old), were collected at autopsy in Jackson, Mississippi. We used a combination of immunohistochemistry, confocal microscopy, and design-based stereology to estimate individual glomerular volume (IGV) and numbers of podocytes, nonepithelial cells (NECs; tuft cells other than podocytes), and parietal epithelial cells (PECs). Podocyte density was calculated. Data are reported as medians and interquartile ranges (IQRs). Glomeruli from children were small and contained 452 podocytes (IQR=335-502), 389 NECs (IQR=265-498), and 146 PECs (IQR=111-206). Adult glomeruli contained significantly more cells than glomeruli from children, including 558 podocytes (IQR=431-746; P<0.01), 1383 NECs (IQR=998-2042; P<0.001), and 367 PECs (IQR=309-673; P<0.001). However, large adult glomeruli showed markedly lower podocyte density (183 podocytes per 10(6) µm(3)) than small glomeruli from adults and children (932 podocytes per 10(6) µm(3); P<0.001). In conclusion, large adult glomeruli contained more podocytes than small glomeruli from children and adults, raising questions about the origin of these podocytes. The increased number of podocytes in large glomeruli does not match the increase in glomerular size observed in adults, resulting in relative podocyte depletion. This may render hypertrophic glomeruli susceptible to pathology.
肾小球大小的增加随着正常身体生长以及在许多病理情况下都会出现。在本研究中，我们确定了肾小球大小与肾小球驻留细胞数量之间的关联，尤其关注足细胞。从密西西比州杰克逊市收集了16名无明显肾脏疾病的男性白种美国人的肾脏，其中包括4名儿童（≤3岁）以确定早期生命的基线值以及12名成年人（≥18岁），这些肾脏是在尸检时获取的。我们联合使用免疫组织化学、共聚焦显微镜和基于设计的体视学方法来估计单个肾小球体积（IGV）以及足细胞、非上皮细胞（NECs；除足细胞外的肾小体细胞）和壁层上皮细胞（PECs）的数量。计算足细胞密度。数据以中位数和四分位数间距（IQRs）表示。儿童的肾小球较小，包含452个足细胞（IQR = 335 - 502）、389个非上皮细胞（IQR = 265 - 498）和146个壁层上皮细胞（IQR = 111 - 206）。成人的肾小球所含细胞明显多于儿童的肾小球，包括558个足细胞（IQR = 431 - 746；P < 0.01）、1383个非上皮细胞（IQR = 998 - 2042；P < 0.00）和367个壁层上皮细胞（IQR = 309 - 673；P < 0.001）。然而，大的成人肾小球显示出足细胞密度（每10(6) µm(3)有183个足细胞）明显低于成人和儿童的小肾小球（每10(6) µm(3)有932个足细胞；P < 0.001）。总之，大的成人肾小球所含足细胞比儿童和成人的小肾小球更多，这引发了关于这些足细胞来源的问题。大肾小球中足细胞数量的增加与成人中观察到的肾小球大小增加不匹配，导致相对足细胞减少。这可能使肥大的肾小球易患病理学改变。
