Université Paris Descartes, Faculté de Médecine, Paris, France.
Service de Physiologie et Explorations Fonctionnelles, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France.
J Clin Endocrinol Metab. 2018 Jun 1;103(6):2319-2328. doi: 10.1210/jc.2018-00123.
The bone-derived hormone fibroblast growth factor (FGF) 23 controls phosphate homeostasis and urinary phosphate excretion. FGF23 plasma levels increase in the early stage of renal insufficiency to prevent hyperphosphatemia. Recent evidence suggests that this increase has effects on cardiac and immune cells that compromise patients' health. Patients with autosomal dominant polycystic kidney disease (ADPKD) have been reported to have higher FGF23 concentrations than other patients with similar renal function. The significance of this finding has remained unknown.
Analyzing the FGF23 plasma levels in 434 patients with ADPKD and 355 control subjects with a measured glomerular filtration rate (mGFR) between 60 and 120 mL/min per 1.73 m2, we confirmed that patients with ADPKD had higher FGF23 plasma concentrations than controls. Remarkably, this difference did not translate into renal phosphate leakage. Using different assays for FGF23, we found that this discrepancy was explained by a predominant increase in the cleaved C-terminal fragment of FGF23, which lacks phosphaturic activity. We found that FGF23 plasma concentration independently correlated with the severity of cystic liver disease in ADPKD. We observed that, in contrast to control liver tissues, the cystic liver from patients with ADPKD markedly expressed FGF23 messenger RNA and protein. In line with this finding, the surgical reduction of polycystic liver mass was associated with a decrease in FGF23 plasma levels independently of any modification in mGFR, phosphate, or iron status.
Our findings demonstrate that severely polycystic livers produce FGF23 and increase levels of circulating FGF23 in patients with ADPKD.
骨源激素成纤维细胞生长因子 23（FGF23）控制着磷酸盐的动态平衡和尿磷酸盐的排泄。在肾功能不全的早期，FGF23 血浆水平会升高，以防止高磷酸盐血症。最近的证据表明，这种升高会对心脏和免疫细胞产生影响，从而损害患者的健康。有报道称，与其他肾功能相似的患者相比，常染色体显性多囊肾病（ADPKD）患者的 FGF23 浓度更高。这一发现的意义尚不清楚。
我们分析了 434 例 ADPKD 患者和 355 例肾小球滤过率（mGFR）在 60 至 120 mL/min/1.73 m2 之间的对照患者的 FGF23 血浆水平，证实 ADPKD 患者的 FGF23 血浆浓度高于对照组。值得注意的是，这种差异并没有转化为肾脏磷酸盐泄漏。使用不同的 FGF23 检测方法，我们发现这种差异是由于缺乏磷排泄活性的 FGF23 裂解 C 端片段的显著增加所解释的。我们发现 FGF23 血浆浓度与 ADPKD 肝囊肿疾病的严重程度独立相关。我们观察到，与对照肝组织相比，ADPKD 的囊性肝组织明显表达 FGF23 信使 RNA 和蛋白。与此发现一致的是，多囊肝体积的手术减少与 FGF23 血浆水平的降低独立相关，而与 mGFR、磷酸盐或铁状态的任何改变无关。
我们的研究结果表明，严重的多囊肝会产生 FGF23，并增加 ADPKD 患者循环中 FGF23 的水平。
