de Zoysa Natasha, Haruhara Kotaro, Nikolic-Paterson David J, Kerr Peter G, Ling Jonathan, Gazzard Sarah E, Puelles Victor G, Bertram John F, Cullen-McEwen Luise A
Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Clayton, VIC, Australia.
Division of Nephrology and Hypertension, Jikei University School of Medicine, Tokyo, Japan.
Front Med (Lausanne). 2024 Mar 6;11:1343161. doi: 10.3389/fmed.2024.1343161. eCollection 2024.
Corticosteroid therapy, often in combination with inhibition of the renin-angiotensin system, is first-line therapy for primary focal and segmental glomerulosclerosis (FSGS) with nephrotic-range proteinuria. However, the response to treatment is variable, and therefore new approaches to indicate the response to therapy are required. Podocyte depletion is a hallmark of early FSGS, and here we investigated whether podocyte number, density and/or size in diagnostic biopsies and/or the degree of glomerulosclerosis could indicate the clinical response to first-line therapy. In this retrospective single center cohort study, 19 participants (13 responders, 6 non-responders) were included. Biopsies obtained at diagnosis were prepared for analysis of podocyte number, density and size using design-based stereology. Renal function and proteinuria were assessed 6 months after therapy commenced. Responders and non-responders had similar levels of proteinuria at the time of biopsy and similar kidney function. Patients who did not respond to treatment at 6 months had a significantly higher percentage of glomeruli with global sclerosis than responders ( < 0.05) and glomerulosclerotic index ( < 0.05). Podocyte number per glomerulus in responders was 279 (203-507; median, IQR), 50% greater than that of non-responders (186, 118-310; 0.05). These findings suggest that primary FSGS patients with higher podocyte number per glomerulus and less advanced glomerulosclerosis are more likely to respond to first-line therapy at 6 months. A podocyte number less than approximately 216 per glomerulus, a GSI greater than 1 and percentage global sclerosis greater than approximately 20% are associated with a lack of response to therapy. Larger, prospective studies are warranted to confirm whether these parameters may help inform therapeutic decision making at the time of diagnosis of primary FSGS.
皮质类固醇疗法通常与肾素 - 血管紧张素系统抑制联合使用，是原发性局灶节段性肾小球硬化（FSGS）伴肾病范围蛋白尿的一线治疗方法。然而，治疗反应存在差异，因此需要新的方法来指示治疗反应。足细胞减少是早期FSGS的一个标志，在此我们研究了诊断性活检中的足细胞数量、密度和/或大小以及/或者肾小球硬化程度是否能够指示对一线治疗的临床反应。在这项回顾性单中心队列研究中，纳入了19名参与者（13名反应者，6名无反应者）。对诊断时获取的活检组织进行处理，采用基于设计的体视学方法分析足细胞数量、密度和大小。在治疗开始6个月后评估肾功能和蛋白尿情况。反应者和无反应者在活检时的蛋白尿水平和肾功能相似。6个月时对治疗无反应的患者，其全球硬化性肾小球的百分比显著高于反应者（<0.05），肾小球硬化指数也显著高于反应者（<0.05）。反应者每个肾小球的足细胞数量为279（203 - 507；中位数，四分位间距），比无反应者（186，118 - 310；P < 0.05）多50%。这些发现表明，每个肾小球足细胞数量较多且肾小球硬化程度较轻的原发性FSGS患者在6个月时更有可能对一线治疗产生反应。每个肾小球足细胞数量少于约216、肾小球硬化指数大于1以及全球硬化百分比大于约20%与治疗无反应相关。需要进行更大规模的前瞻性研究来证实这些参数是否有助于在原发性FSGS诊断时为治疗决策提供参考。
