Glomerulomegaly and focal segmental glomerulosclerosis are histopathological hallmarks of obesity-related glomerulopathy (ORG). Podocyte injury and subsequent depletion are regarded as key processes in the development of these glomerular lesions in patients with ORG, but their impact on long-term kidney outcome is undetermined. Here, we correlated clinicopathological findings and podocyte depletion retrospectively in patients with ORG. Relative (podocyte density) and absolute (podocyte number per glomerulus) measures of podocyte depletion were estimated using model-based stereology in 46 patients with ORG. The combined endpoint of kidney outcomes was defined as a 30% decline in estimated glomerular filtration rate (eGFR) or kidney failure. Patients with lower podocyte density were predominantly male and had larger body surface area, greater proteinuria, fewer non-sclerotic glomeruli, larger glomeruli and higher single-nephron eGFR. During a median follow-up of 4.1 years, 18 (39%) patients reached endpoint. Kidney survival in patients with lower podocyte density was significantly worse than in patients with higher podocyte density. However, there was no difference in kidney survival between patient groups based on podocyte number per glomerulus. Cox hazard analysis showed that podocyte density, but not podocyte number per glomerulus, was associated with the kidney outcomes after adjustment for clinicopathological confounders. Thus, our study demonstrates that a relative depletion of podocytes better predicts long-term kidney outcomes than does absolute depletion of podocytes. Hence, the findings implicate mismatch between glomerular enlargement and podocyte number as a crucial determinant of disease progression in ORG.

中文翻译：

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足细胞密度作为肥胖相关肾小球病长期肾脏结局的预测因子


肾小球肿大和局灶节段性肾小球硬化是肥胖相关肾小球病（ORG）的组织病理学标志。足细胞损伤和随后的耗竭被认为是 ORG 患者肾小球病变发展的关键过程，但它们对长期肾脏结果的影响尚未确定。在这里，我们回顾性地将 ORG 患者的临床病理学结果与足细胞耗竭相关联。使用基于模型的体视学对 46 名 ORG 患者进行足细胞消耗的相对（足细胞密度）和绝对（每个肾小球足细胞数量）测量。肾脏结局的综合终点定义为估计肾小球滤过率 (eGFR) 下降 30% 或肾衰竭。足细胞密度较低的患者主要是男性，体表面积较大，蛋白尿较多，非硬化性肾小球较少，肾小球较大，单肾单位 eGFR 较高。在中位随访 4.1 年期间，18 名患者 (39%) 达到终点。足细胞密度较低的患者的肾脏存活率明显低于足细胞密度较高的患者。然而，根据每个肾小球的足细胞数量，患者组之间的肾脏存活率没有差异。 Cox 风险分析表明，在调整临床病理混杂因素后，足细胞密度（而非每个肾小球的足细胞数量）与肾脏结果相关。因此，我们的研究表明，足细胞的相对消耗比足细胞的绝对消耗更好地预测长期肾脏结果。因此，研究结果表明肾小球增大和足细胞数量之间的不匹配是 ORG 疾病进展的关键决定因素。